Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
0  structures 110  species 0  interactions 136  sequences 6  architectures

Family: Med30 (PF11315)

Summary: Mediator complex subunit 30

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 "MED30". More...

MED30 Edit Wikipedia article

MED30
Identifiers
Aliases MED30, MED30S, THRAP6, TRAP25, mediator complex subunit 30
External IDs MGI: 1917040 HomoloGene: 12329 GeneCards: MED30
Genetically Related Diseases
Kawasaki disease[1]
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001282986
NM_080651

NM_027212

RefSeq (protein)

NP_001269915
NP_542382

NP_081488.1
NP_081488

Location (UCSC) Chr 8: 117.52 – 117.54 Mb Chr 15: 52.71 – 52.73 Mb
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse
Med30
Identifiers
Symbol Med30
Pfam PF11315
InterPro IPR021019

Mediator of RNA polymerase II transcription subunit 30 is an enzyme that in humans is encoded by the MED30 gene.[4] It represents subunit Med30 of the Mediator complex and is metazoan-specific,[5] having no homologues in yeasts.

Interactions

MED30 has been shown to interact with MED22.[6]

References

  1. ^ "Diseases that are genetically associated with MED30 view/edit references on wikidata". 
  2. ^ "Human PubMed Reference:". 
  3. ^ "Mouse PubMed Reference:". 
  4. ^ "Entrez Gene: THRAP6 thyroid hormone receptor associated protein 6". 
  5. ^ Baek HJ, Malik S, Qin J, Roeder RG (Apr 2002). "Requirement of TRAP/mediator for both activator-independent and activator-dependent transcription in conjunction with TFIID-associated TAF(II)s". Molecular and Cellular Biology. 22 (8): 2842–52. doi:10.1128/MCB.22.8.2842-2852.2002. PMC 133729Freely accessible. PMID 11909976. 
  6. ^ 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 (Apr 2003). "Identification of mammalian Mediator subunits with similarities to yeast Mediator subunits Srb5, Srb6, Med11, and Rox3". The Journal of Biological Chemistry. 278 (17): 15123–7. doi:10.1074/jbc.C300054200. PMID 12584197. 

Further reading


This article incorporates text from the public domain Pfam and InterPro IPR021019

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

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[1][2] in the lab of Roger D. Kornberg, winner of the 2006 Nobel Prize in Chemistry. Mediator[a] complexes interact with transcription factors and RNA polymerase II. The main (but not exclusive) 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

Mediator Structural Model (2015)

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]

Structural model of mediator with RNA polymerase II

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

Model of mediator with some transcription factors, Pol II and DNA

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]

Structure

Mediator complex architecture with focus on Med 14

The yeast mediator complex is approximately as massive as a small subunit of a eukaryotic ribosome. Mammalian mediator complexes are slightly larger.[3] A great deal is known about the physical arrangement of the subunits, but a review of all of them is beyond the scope of this article. One important example is the Med 14 subunit structure.

Mediator subunits have many intrinsically disordered regions, 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. Only one of each pair can associate with the other kinase module subunits, meaning that there are 8 different kinase modules in vertebrates.[3][6] In contrast to the situation in yeast, it was found that vertebrate mediator associated with the kinase module containing the MED13 paralog (MED13L) does contain MED26.[6]

There is a report that mediator forms stable associations with a particular type of non-coding RNA, ncRNA-a.[7][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.[7] Thus, the structure of a mediator complex can be augmented by RNA as well as proteinaceous transcription factors.[3]

Function

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 synthesis

The preinitiation complex, which contains mediator, transcription factors, a nucleosome[8][9][g] and RNA polyemrase 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 transcripts of tRNAs[10]

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[7] 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.[11] In both human cells and Caenorhabditis elegans MED15 is involved in lipid homeostasis through the pathway involving SREBPs[12] In the model plant Arabidopsis thaliana the ortholog of MED15 is required for signaling by a plant hormone.[13] 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.[14][15][16][17][18] [19][20][21][22] [23][24] 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]

MED 1

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.[25] The tumor suppressor miR-137 also regulates MED1.[26]

Mouse embryonic development

Null mutants die at an early gestational age (embryonic day 11.5).[27][28] 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[28]

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 controling the timing of events of meiosis in male mice.[29] Conditional mutants in keratinocytes show differences in skin wound healing.[30] A conditional mutant in mice was found to change dental epithelium into epidermal epithelium, which caused hair to grow associated with the incisors.[31]

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.[32]

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.[32][33]

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 a MED2
Med3 a PGD1
MED4 MED4 MED4 MED4 med4
Med5 a NUT1
MED6 MED6 MDT-6 MED6 MED6 med6
MED7 MED7 MDT-7/let-49 MED7 MED7 med7
MED8 MED8 MDT-8 MED8 MED8 med8
Med9 MED9 MED9 CSE2
Med10 MED10 MDT-10 NUT2 med10
Med11 MED11 MDT-11 MED11 MED11 med11
MED12 MED12 MDT-12/dpy-22 MED12 SRB8 srb8
Med12L MED12L
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 b
MED16 MED16 MED16 SIN4
MED17 MED17 MDT-17 MED17 SRB4 med17
Med18 MED18 MDT-18 MED18 SRB5 med18
Med19 MED19 MDT-19 MED19 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
MED24 MED24 MED24
MED25 MED25 MED25
MED26 MED26 MED26
MED27 MED27 MED27 med27
MED28 MED28 MED28
Med29 MED29 MDT-19 MED29 MED29
MED30 MED30 MED30
MED31 MED31 MDT-31 MED31 SOH1 med31
CCNC CCNC cic-1 CycC SSN8 pch1
CDK8 CDK8 cdk-8 Cdk8 SSN3 srb10
  • a Fungal-specific
  • b Protein-name in Sch. pombe

Notes

  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 February 16, 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.

References

  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. 
  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. doi:10.1038/350436a0. PMID 2011193. 
  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. 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. 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. PMID 21468301. 
  6. ^ a b Daniels, DL; Ford, M; Schwinn MK, Benink H, Galbraith MD; et al. (July 11, 2013). "Mutual Exclusivity of MED12/MED12L, MED13/13L, and CDK8/19 Paralogs Revealed within the CDK-Mediator Kinase Module." (PDF). doi:10.4172/jpb.S2-004. 
  7. ^ a b c Lai, F; et al. (02/2013). "Activating RNAs associate with mediator to enhance chromatin architecture and transcription". Nature. 494 (7438): 497–501. doi:10.1038/nature11884. PMID 23417068.  Check date values in: |date= (help)
  8. ^ 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. PMID 28137832. 
  9. ^ Kornberg, RD. "The Molecular Basis of Eukaryotic Transcription". YouTube. Israel Institute for Advanced Studies. Retrieved 17 February 2017. 
  10. ^ 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. 
  11. ^ 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. doi:10.1038/nature00969. PMID 12167862. 
  12. ^ 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. doi:10.1038/nature04942. PMID 16799563. 
  13. ^ 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. PMID 23064321. 
  14. ^ Clark AD, Oldenbroek M, Boyer TG (2015). "Mediator kinase module and human tumorigenesis.". Crit Rev Biochem Mol Biol. 50 (5): 393–426. PMID 26182352. 
  15. ^ 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. 
  16. ^ 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. 
  17. ^ 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. 
  18. ^ 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. 
  19. ^ 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. PMID 23727265. 
  20. ^ 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. 
  21. ^ 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. 
  22. ^ 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. 
  23. ^ 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. PMID 21840410. 
  24. ^ Lyons MJ. (2008). MED12-Related Disorders. (08/11/2016 ed.). ncbi.nlm.nih.gov/books. 
  25. ^ 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. 
  26. ^ 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. PMID 26461474. 
  27. ^ 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. 
  28. ^ 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. 
  29. ^ 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. PMID 25778538. 
  30. ^ 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. doi:10.1371/journal.pone.0102271. PMID 25122137. 
  31. ^ 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. doi:10.1371/journal.pone.0099991. PMID 24949995. 
  32. ^ a b 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. 
  33. ^ 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 30 Provide feedback

Med30 is a metazoan-specific subunit of Mediator, having no homologues in yeasts.

Literature references

  1. Bourbon HM, Aguilera A, Ansari AZ, Asturias FJ, Berk AJ, Bjorklund S, Blackwell TK, Borggrefe T, Carey M, Carlson M, Conaway JW, Conaway RC, Emmons SW, Fondell JD, Freedman LP, Fukasawa T, Gustafsson CM, Han M, He X, Herman PK, Hinnebusch AG, Holmberg S, , Mol Cell. 2004;14:553-557.: A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase II. PUBMED:15175151 EPMC:15175151

  2. Baek HJ, Malik S, Qin J, Roeder RG; , Mol Cell Biol. 2002;22:2842-2852.: Requirement of TRAP/mediator for both activator-independent and activator-dependent transcription in conjunction with TFIID-associated TAF(II)s. PUBMED:11909976 EPMC:11909976


This tab holds annotation information from the InterPro database.

InterPro entry IPR021019

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.

Med30 is a metazoan-specific subunit of Mediator [PUBMED:11909976], having no homologues in yeasts.

Domain organisation

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

Loading domain graphics...

Alignments

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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

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.

  Seed
(19)
Full
(136)
Representative proteomes UniProt
(256)
NCBI
(494)
Meta
(0)
RP15
(45)
RP35
(73)
RP55
(109)
RP75
(135)
Jalview View  View  View  View  View  View  View  View   
HTML View  View               
PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(19)
Full
(136)
Representative proteomes UniProt
(256)
NCBI
(494)
Meta
(0)
RP15
(45)
RP35
(73)
RP55
(109)
RP75
(135)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(19)
Full
(136)
Representative proteomes UniProt
(256)
NCBI
(494)
Meta
(0)
RP15
(45)
RP35
(73)
RP55
(109)
RP75
(135)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download   Download    

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...

Trees

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.

Note: You can also download the data file for the tree.

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_28118 (release 23.0)
Previous IDs: none
Type: Domain
Author: Coggill P
Number in seed: 19
Number in full: 136
Average length of the domain: 133.50 aa
Average identity of full alignment: 47 %
Average coverage of the sequence by the domain: 64.98 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 28.1 28.1
Trusted cut-off 32.4 29.7
Noise cut-off 25.9 23.9
Model length: 147
Family (HMM) version: 6
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.