MED26

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.

MED26
Identifiers
Aliases	MED26, CRSP7, CRSP70, mediator complex subunit 26
External IDs	OMIM: 605043; MGI: 1917875; HomoloGene: 68417; GeneCards: MED26; OMA:MED26 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.11 Start 16,574,907 bp[1] End 16,629,062 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 B3.3 Start 73,248,405 bp[2] End 73,302,114 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sperm amniotic fluid buccal mucosa cell tibialis anterior muscle nipple skin of arm mucosa of ileum left testis right testis secondary oocyte Top expressed in seminiferous tubule secondary oocyte primary oocyte spermatocyte zygote spermatid granulocyte muscle of thigh medullary collecting duct renal corpuscle More reference expression data BioGPS n/a
Gene ontology Molecular function transcription coactivator activity transcription coregulator activity protein binding Cellular component mediator complex nucleus nucleoplasm core mediator complex Biological process regulation of transcription by RNA polymerase II transcription initiation from RNA polymerase II promoter regulation of transcription, DNA-templated transcription, DNA-templated positive regulation of nucleic acid-templated transcription positive regulation of gene expression Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9441 70625 Ensembl ENSG00000105085 ENSMUSG00000045248 UniProt O95402 Q7TN02 RefSeq (mRNA) NM_004831 NM_027485 RefSeq (protein) NP_004822 NP_081761 Location (UCSC) Chr 19: 16.57 – 16.63 Mb Chr 8: 73.25 – 73.3 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Med26
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
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Mediator subunit 26 Middle domain
Identifiers
Symbol	Med26_M
Pfam	PF15694
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Mediator subunit 26 C-terminal domain
Identifiers
Symbol	Med26_C
Pfam	PF15693
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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][10] Specific examples are listed below:

• 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.^[11]
• TFIIS, which rescues RNA polymerase II from backtracked pause states.

The N-terminal domain of MED26 is a protein fold known as a TFIIS N-terminal domain (or TND).^[8] It is a compact five-helix bundle. The hydrophobic core residues of helices 2, 3, and 4 are well conserved among TFIIS domains, although helix 1 is less conserved.^[10]

Interactions

MED26 has been shown to interact with MED8,^[12] Cyclin-dependent kinase 8,^[12] POLR2A,^[12] MED12^[12] and MED28.^[12] 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.^[13]