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0  structures 1031  species 0  interactions 1694  sequences 32  architectures

Family: Med13_C (PF06333)

Summary: Mediator complex subunit 13 C-terminal domain

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 "MED13". More...

MED13 Edit Wikipedia article

MED13
Identifiers
Aliases MED13, ARC250, DRIP250, HSPC221, THRAP1, TRAP240, mediator complex subunit 13
External IDs MGI: 3029632 HomoloGene: 21067 GeneCards: MED13
Gene location (Human)
Chromosome 17 (human)
Chr. Chromosome 17 (human)[1]
Chromosome 17 (human)
Genomic location for MED13
Genomic location for MED13
Band n/a Start 61,942,605 bp[1]
End 62,065,282 bp[1]
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005121

NM_001080931

RefSeq (protein)

NP_005112

NP_001074400

Location (UCSC) Chr 17: 61.94 – 62.07 Mb Chr 17: 86.27 – 86.36 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Mediator complex subunit 13 is a protein that in humans is encoded by the MED13 gene.[5][6]

Function

This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. The product of this gene is proposed to form a sub-complex with MED12, cyclin C, and CDK8 that can negatively regulate transactivation by mediator.[5]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000108510 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034297 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ a b "Entrez Gene: Mediator complex subunit 13". Retrieved 2012-05-11. 
  6. ^ Tuchin DA, Erve PR, Schumer W (1976). "Prevention of endotoxin--induced irreversible platelet aggregation in vitro". Surgical Forum. 27 (62): 22–3. PMID 1019863. 

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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

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 13 C-terminal domain Provide feedback

Mediator is a large complex of up to 33 proteins that is conserved from plants through fungi to humans - the number and representation of individual subunits varying with species [1-2]. It is arranged into four different sections, a core, a head, a tail and a kinase-activity part, and the number of subunits within each of these is what varies with species. Overall, Mediator regulates the transcriptional activity of RNA polymerase II but it would appear that each of the four different sections has a slightly different function. Med13 is part of the ancillary kinase module, together with Med12, CDK8 and CycC, which in yeast is implicated in transcriptional repression, though most of this activity is likely attributable to the CDK8 kinase. The large Med12 and Med13 proteins are required for specific developmental processes in Drosophila, zebrafish, and Caenorhabditis elegans but their biochemical functions are not understood [4]. This domain is also identified as an RNaseH domain of the medPIWI PIWI/Argonaute module. medPIWI is the core domain found in the Med13 protein. The medPIWI module in Med13 is predicted to bind double-stranded nucleic acids, triggering the experimentally-observed conformational switch in the CDK8 subcomplex which regulates the Mediator complex [5].

Literature references

  1. Samuelsen CO, Baraznenok V, Khorosjutina O, Spahr H, Kieselbach T, Holmberg S, Gustafsson CM; , Proc Natl Acad Sci U S A 2003;100:6422-6427.: TRAP230/ARC240 and TRAP240/ARC250 Mediator subunits are functionally conserved through evolution. PUBMED:12738880 EPMC:12738880

  2. 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

  3. 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; , Mol Cell. 2004;14:685-691.: A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. PUBMED:15175163 EPMC:15175163

  4. Carrera I, Janody F, Leeds N, Duveau F, Treisman JE; , Proc Natl Acad Sci U S A. 2008;105:6644-6649.: Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13. PUBMED:18451032 EPMC:18451032

  5. Burroughs AM, Iyer LM, Aravind L;, Biol Direct. 2013;8:13.: Two novel PIWI families: roles in inter-genomic conflicts in bacteria and Mediator-dependent modulation of transcription in eukaryotes. PUBMED:23758928 EPMC:23758928


This tab holds annotation information from the InterPro database.

InterPro entry IPR009401

This entry represents the C-terminal domain of Med13. This domain is also identified as an RNaseH domain of the medPIWI PIWI/Argonaute module. medPIWI is the core domain found in the Med13 protein. The medPIWI module in Med13 is predicted to bind double-stranded nucleic acids, triggering the experimentally-observed conformational switch in the CDK8 subcomplex which regulates the Mediator complex [PUBMED:23758928]. Med13 is a component of the SRB8-11 complex. The SRB8-11 complex is a regulatory module of the Mediator complex, which may be involved in the transcriptional repression of a subset of genes regulated by Mediator. It acts by inhibiting the association of the Mediator complex with RNA polymerase II to form the holoenzyme complex [PUBMED:12738880].

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

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Alignments

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(89)
Full
(1694)
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(2719)
NCBI
(3798)
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(206)
RP35
(697)
RP55
(1270)
RP75
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  Seed
(89)
Full
(1694)
Representative proteomes UniProt
(2719)
NCBI
(3798)
Meta
(0)
RP15
(206)
RP35
(697)
RP55
(1270)
RP75
(1776)
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  Seed
(89)
Full
(1694)
Representative proteomes UniProt
(2719)
NCBI
(3798)
Meta
(0)
RP15
(206)
RP35
(697)
RP55
(1270)
RP75
(1776)
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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

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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.

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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: [1]
Previous IDs: TRAP240; TRAP_240kDa; Med13;
Type: Domain
Sequence Ontology: SO:0000417
Author: Studholme DJ , Wood V
Number in seed: 89
Number in full: 1694
Average length of the domain: 336.80 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 19.63 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.1 26.1
Trusted cut-off 26.1 26.1
Noise cut-off 25.5 25.6
Model length: 331
Family (HMM) version: 13
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