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0  structures 74  species 0  interactions 106  sequences 4  architectures

Family: Med26_M (PF15694)

Summary: Mediator complex subunit 26 middle domain

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This is the Wikipedia entry entitled "MED26". More...

MED26 Edit Wikipedia article

MED26
Identifiers
Aliases MED26, CRSP7, CRSP70, mediator complex subunit 26
External IDs MGI: 1917875 HomoloGene: 68417 GeneCards: MED26
Gene location (Human)
Chromosome 19 (human)
Chr. Chromosome 19 (human)[1]
Chromosome 19 (human)
Genomic location for MED26
Genomic location for MED26
Band n/a Start 16,574,907 bp[1]
End 16,629,062 bp[1]
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004831

NM_027485

RefSeq (protein)

NP_004822

NP_081761

Location (UCSC) Chr 19: 16.57 – 16.63 Mb Chr 19: 72.49 – 72.55 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
Med26
PDB 1wjt EBI.jpg
solution structure of the n-terminal domain i of mouse transcription elongation factor s-ii protein 3
Identifiers
Symbol Med26 N-terminal domain
Pfam PF08711
InterPro IPR017923
Mediator subunit 26 Middle domain
Identifiers
Symbol Med26_M
Pfam PF15694
Mediator subunit 26 C-terminal domain
Identifiers
Symbol Med26_C
Pfam PF15693

Mediator of RNA polymerase II transcription subunit 26 is an enzyme that in humans is encoded by the MED26 gene.[5][6] It forms part of the Mediator complex.

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.[6]

Activity

MED26 is a transcription elongation factor that increases the overall transcription rate of RNA polymerase II by reactivating transcription elongation complexes that have arrested transcription. It does this through recruiting ELL/EAF- and P-TEFb- containing complexes to promoters via a direct interaction with the N-terminal domain (NTD). The MED26 NTD also binds TFIID, and TFIID and elongation complexes interact with MED26 through overlapping binding sites. [7] MED26 NTD may function as a molecular switch contributing to the transition of Pol II into productive elongation.

The three structural domains of TFIIS are conserved from yeast to human. The 80 or so N-terminal residues form a protein interaction domain containing a conserved motif, which has been called the LW motif because of the invariant leucine and tryptophan residues it contains. Although the N-terminal domain is not needed for transcriptional activity, a similar sequence has been identified in other transcription factors and proteins that are predominantly nuclear localized,:[8][9]

  • MED26 (also known as CRSP70 and ARC70), a subunit of the Mediator complex, which is required for the activity of the enhancer-binding protein Sp1.
  • Elongin A, a subunit of a transcription elongation factor previously known as SIII. It increases the rate of transcription by suppressing transient pausing of the elongation complex.
  • PPP1R10, a nuclear regulatory subunit of protein phosphatase 1 that was previously known as p99, FB19 or PNUTS.
  • PIBP, a small hypothetical protein that could be a phosphoinositide binding protein.
  • IWS1, which is thought to function in both transcription initiation and elongation. The TFIIS N-terminal domain is a compact four-helix bundle. The hydrophobic core residues of helices 2, 3, and 4 are well conserved among TFIIS domains, although helix 1 is less conserved.[9]

Interactions

MED26 has been shown to interact with MED8,[10] Cyclin-dependent kinase 8,[10] POLR2A,[10] MED12[10] and MED28.[10] It also acts synergistically to mediate the interaction between REST (a Kruppel-type zinc finger transcription factor that binds to a 21-bp RE1 silencing element present in over 900 human genes) and Mediator.[11]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000105085 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045248 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  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. PMID 9989412. doi:10.1038/17141. 
  6. ^ a b "Entrez Gene: CRSP7 cofactor required for Sp1 transcriptional activation, subunit 7, 70kDa". 
  7. ^ Takahashi H, Parmely TJ, Sato S, Tomomori-Sato C, Banks CA, Kong SE, et al. (2011). "Human mediator subunit MED26 functions as a docking site for transcription elongation factors.". Cell. 146 (1): 92–104. PMC 3145325Freely accessible. PMID 21729782. doi:10.1016/j.cell.2011.06.005. 
  8. ^ Booth V, Koth CM, Edwards AM, Arrowsmith CH (October 2000). "Structure of a conserved domain common to the transcription factors TFIIS, elongin A, and CRSP70". J. Biol. Chem. 275 (40): 31266–8. PMID 10811649. doi:10.1074/jbc.M002595200. 
  9. ^ a b Ling Y, Smith AJ, Morgan GT (2006). "A sequence motif conserved in diverse nuclear proteins identifies a protein interaction domain utilised for nuclear targeting by human TFIIS". Nucleic Acids Res. 34 (8): 2219–29. PMC 1450333Freely accessible. PMID 16648364. doi:10.1093/nar/gkl239. 
  10. ^ a b c d e 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 (June 2004). "A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology". Mol. Cell. 14 (5): 685–91. PMID 15175163. doi:10.1016/j.molcel.2004.05.006. 
  11. ^ Ding N, Tomomori-Sato C, Sato S, Conaway RC, Conaway JW, Boyer TG (January 2009). "MED19 and MED26 are synergistic functional targets of the RE1 silencing transcription factor in epigenetic silencing of neuronal gene expression". J. Biol. Chem. 284 (5): 2648–56. PMC 2631966Freely accessible. PMID 19049968. doi:10.1074/jbc.M806514200. 

This article incorporates text from the public domain Pfam and InterPro IPR017923

Further reading

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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 26 middle domain Provide feedback

Med26_M is the middle domain of subunit 26 of Mediator. Med19 and Med26 act synergistically to mediate the interaction between REST (a Kruppel-type zinc finger transcription factor that binds to a 21-bp RE1 silencing element present in over 900 human genes) and Mediator [1].

Literature references

  1. Ding N, Tomomori-Sato C, Sato S, Conaway RC, Conaway JW, Boyer TG;, J Biol Chem. 2009;284:2648-2656.: MED19 and MED26 are synergistic functional targets of the RE1 silencing transcription factor in epigenetic silencing of neuronal gene expression. PUBMED:19049968 EPMC:19049968

  2. Takahashi H, Parmely TJ, Sato S, Tomomori-Sato C, Banks CA, Kong SE, Szutorisz H, Swanson SK, Martin-Brown S, Washburn MP, Florens L, Seidel CW, Lin C, Smith ER, Shilatifard A, Conaway RC, Conaway JW;, Cell. 2011;146:92-104.: Human mediator subunit MED26 functions as a docking site for transcription elongation factors. PUBMED:21729782 EPMC:21729782


This tab holds annotation information from the InterPro database.

InterPro entry IPR031417

This entry represents the middle domain of subunit 26 of Mediator (Med26). Med19 and Med26 act synergistically to mediate the interaction between Mediator and REST, a Kruppel-type zinc finger transcription factor that binds to a 21-bp RE1 silencing element present in over 900 human genes [PUBMED:19049968].

Domain organisation

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(17)
Full
(106)
Representative proteomes UniProt
(182)
NCBI
(503)
Meta
(0)
RP15
(11)
RP35
(42)
RP55
(84)
RP75
(103)
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  Seed
(17)
Full
(106)
Representative proteomes UniProt
(182)
NCBI
(503)
Meta
(0)
RP15
(11)
RP35
(42)
RP55
(84)
RP75
(103)
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Curation View help on the curation process

Seed source: Pfam-B_25390 (release 26.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Coggill P
Number in seed: 17
Number in full: 106
Average length of the domain: 215.80 aa
Average identity of full alignment: 49 %
Average coverage of the sequence by the domain: 39.60 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 34.6 30.2
Noise cut-off 19.9 26.2
Model length: 255
Family (HMM) version: 5
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