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18  structures 794  species 10  interactions 966  sequences 22  architectures

Family: Med8 (PF10232)

Summary: Mediator of RNA polymerase II transcription complex subunit 8

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 "MED8". More...

MED8 Edit Wikipedia article

MED8
Identifiers
Aliases MED8, ARC32, mediator complex subunit 8
External IDs MGI: 1915269 HomoloGene: 10560 GeneCards: MED8
Gene location (Human)
Chromosome 1 (human)
Chr. Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for MED8
Genomic location for MED8
Band 1p34.2 Start 43,383,917 bp[1]
End 43,389,808 bp[1]
RNA expression pattern
PBB GE MED8 213127 s at fs.png

PBB GE MED8 213126 at fs.png

PBB GE MED8 213696 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_201542
NM_001001653
NM_052877

NM_001290688
NM_020000
NM_173719

RefSeq (protein)

NP_001001653
NP_443109
NP_963836

NP_001277617
NP_064384
NP_776067

Location (UCSC) Chr 1: 43.38 – 43.39 Mb Chr 4: 118.41 – 118.42 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Mediator of RNA polymerase II transcription subunit 8 is an enzyme that in humans is encoded by the MED8 gene.[5][6][7]

Function

This gene encodes a protein that is one of more than 20 subunits of the mediator complex, first identified in S. cerevisiae, that is required for activation of transcription. The product of this gene also interacts with elongins B and C, and CUL2 and RBX1, to reconstitute a ubiquitin ligase. Five alternative transcripts encoding four isoforms have been described.[7]

Interactions

MED8 has been shown to interact with MED26.[8]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000159479 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000006392 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Brower CS, Sato S, Tomomori-Sato C, Kamura T, Pause A, Stearman R, Klausner RD, Malik S, Lane WS, Sorokina I, Roeder RG, Conaway JW, Conaway RC (Aug 2002). "Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase". Proc Natl Acad Sci U S A. 99 (16): 10353–8. doi:10.1073/pnas.162424199. PMC 124918Freely accessible. PMID 12149480. 
  6. ^ Jiang YW, Veschambre P, Erdjument-Bromage H, Tempst P, Conaway JW, Conaway RC, Kornberg RD (Aug 1998). "Mammalian mediator of transcriptional regulation and its possible role as an end-point of signal transduction pathways". Proc Natl Acad Sci U S A. 95 (15): 8538–43. doi:10.1073/pnas.95.15.8538. PMC 21111Freely accessible. PMID 9671713. 
  7. ^ a b "Entrez Gene: MED8 mediator of RNA polymerase II transcription, subunit 8 homolog (S. cerevisiae)". 
  8. ^ 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". Mol. Cell. 14 (5): 685–91. doi:10.1016/j.molcel.2004.05.006. PMID 15175163. 

Further reading


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 of RNA polymerase II transcription complex subunit 8 Provide feedback

Arc32, or Med8, is one of the subunits of the Mediator complex of RNA polymerase II. The region conserved contains two alpha helices putatively necessary for binding to other subunits within the core of the Mediator complex [1]. The N-terminus of Med8 binds to the essential core Head part of Mediator and the C-terminus hinges to Med18 on the non-essential part of the Head that also includes Med20 [3].

Literature references

  1. 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

  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. 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 IPR019364

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.

Arc32, or Med8, is one of the subunits of the Mediator complex of RNA polymerase II. The region conserved contains two alpha helices putatively necessary for binding to other subunits within the core of the Mediator complex. The N terminus of Med8 binds to the essential core Head part of Mediator and the C terminus hinges to Med18 on the non-essential part of the Head that also includes Med20 [PUBMED:18381891].

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

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...

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  Seed
(37)
Full
(966)
Representative proteomes UniProt
(1624)
NCBI
(1872)
Meta
(1)
RP15
(148)
RP35
(338)
RP55
(605)
RP75
(969)
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  Seed
(37)
Full
(966)
Representative proteomes UniProt
(1624)
NCBI
(1872)
Meta
(1)
RP15
(148)
RP35
(338)
RP55
(605)
RP75
(969)
Alignment:
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  Seed
(37)
Full
(966)
Representative proteomes UniProt
(1624)
NCBI
(1872)
Meta
(1)
RP15
(148)
RP35
(338)
RP55
(605)
RP75
(969)
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Gzipped Download   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: KOGs (KOG3583)
Previous IDs: Arc32;
Type: Family
Sequence Ontology: SO:0100021
Author: KOGs, Finn RD , Coggill P
Number in seed: 37
Number in full: 966
Average length of the domain: 226.60 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 78.79 %

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 27.2 27.2
Trusted cut-off 27.2 27.2
Noise cut-off 26.9 27.1
Model length: 233
Family (HMM) version: 10
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 10 interactions for this family. More...

Med18 Med22 Med18 Med11 Med6 Med6 Med17 Med11 Med17 RNA_pol_Rpb1_R

Structures

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 Med8 domain has been found. There are 18 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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