Details for: MED26

Gene ID: 9441

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: MED26

Ensembl ID: ENSG00000105085

Description: mediator complex subunit 26

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.83
    rCSI 2.67%
    PRS 99.81
  • neural progenitor cell CL0011020
    CSI 3.42
    rCSI 15.03%
    PRS 96.21
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.51
    rCSI 3.13%
    PRS 97.61
  • basal cell CL0000646
    CSI 2.29
    rCSI 3.06%
    PRS 99.34
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.23
    rCSI 4.99%
    PRS 98.03
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.08
    rCSI 3.68%
    PRS 97.86
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.21
    rCSI 2.94%
    PRS 97.16

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [MED26](/details-gene/9441) (Mediator Complex Subunit 26) is a protein-coding gene that encodes a core component of the Mediator complex, a large, evolutionarily conserved coactivator essential for regulating RNA polymerase II transcription. Functionally, it acts as a transcriptional coactivator, playing a fundamental role in processes such as the assembly of the preinitiation complex and the positive regulation of gene expression. **Overall**, expression data highlights its particular significance in diverse and highly specialized cell types, including [plasmacytoid dendritic cell, human](/details-cell/CL0001058) and various neuronal populations like [neural progenitor cell](/details-cell/CL0011020), suggesting a critical role in both innate immunity and neurodevelopment. ## Cellular Roles and Expression Landscape [MED26](/details-gene/9441) is a broadly important transcriptional regulator, with data indicating it has particularly high significance in specific cellular contexts. Its highest significance score is observed in [plasmacytoid dendritic cell, human](/details-cell/CL0001058) (CSI: 3.83), a key cell type in antiviral innate immunity, suggesting a specialized function in mediating rapid, large-scale transcriptional responses to pathogens. A second major functional axis for [MED26](/details-gene/9441) appears to be within the central nervous system. The gene shows high significance in [neural progenitor cell](/details-cell/CL0011020) (CSI: 3.42), as well as in more mature neuronal subtypes, including [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 2.51), [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064) (CSI: 2.08), and [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040) (CSI: 1.21). Its importance is also noted in glial cells, specifically [astrocyte of the cerebral cortex](/details-cell/CL0002605) (CSI: 2.23). This pattern suggests that [MED26](/details-gene/9441) is integral to the transcriptional programs governing both neurodevelopment and the maintenance of specialized neuronal and glial functions. Finally, its relevance in [basal cell](/details-cell/CL0000646) (CSI: 2.29) points to a role in epithelial tissue homeostasis and regeneration. ## Pathways and Molecular Function As a subunit of the [Mediator complex](/details-go/GO:0016592), [MED26](/details-gene/9441) is central to the process of eukaryotic transcription. Gene Ontology annotations confirm its role as a [transcription coactivator activity](/details-go/GO:0003713) located within the [nucleus](/details-go/GO:0005634), where it participates in [rna polymerase ii preinitiation complex assembly](/details-go/GO:0051123) and facilitates [positive regulation of transcription elongation by rna polymerase ii](/details-go/GO:0032968). Its function is crucial for the expression of a wide array of genes, as evidenced by early studies identifying the Mediator complex as a requirement for enhancer-binding proteins [Link](https://doi.org/10.1038/17141). Reactome pathway analysis further contextualizes its function. [MED26](/details-gene/9441) is a key component of the [Gene expression (transcription)](/details-reactome/R-HSA-74160) and [Rna polymerase ii transcription](/details-reactome/R-HSA-73857) pathways. The data also reveals more specialized roles. Its involvement in [Viral infection pathways](/details-reactome/R-HSA-9824446), particularly the [Respiratory syncytial virus infection pathway](/details-reactome/R-HSA-9820952), is highly consistent with its prominent expression in [plasmacytoid dendritic cell, human](/details-cell/CL0001058), which are sentinel cells for viral detection. Furthermore, its participation in pathways like [Adipogenesis](/details-reactome/R-HSA-9843745) and [Developmental biology](/details-reactome/R-HSA-1266738) aligns with its importance in progenitor cells and metabolic regulation. ## Research Directions The available data suggests that while [MED26](/details-gene/9441) is a general transcription factor, its functional impact is particularly pronounced in specific biological contexts, such as antiviral immunity and neurodevelopment. This specificity raises important questions about its regulatory roles. **Proposed Hypotheses:** 1. Given its top significance in [plasmacytoid dendritic cell, human](/details-cell/CL0001058) and its linkage to viral infection pathways, [MED26](/details-gene/9441) may function as a rate-limiting coactivator for interferon-regulatory factors (IRFs), such as IRF7, thereby being essential for the massive production of type I interferons that defines the pDC antiviral response. 2. The high significance of [MED26](/details-gene/9441) in [neural progenitor cell](/details-cell/CL0011020) and various differentiated neuronal subtypes suggests it is required for neuronal fate specification. It may mediate the switch from progenitor maintenance to differentiation by bridging key lineage-determining transcription factors (e.g., NEUROG2, ASCL1) to the core transcriptional machinery. **Experimental Approach:** To test the first hypothesis regarding its role in pDCs, one could employ a loss-of-function study. CRISPR-Cas9-mediated knockout of [MED26](/details-gene/9441) could be performed in primary human pDCs or a representative cell line (e.g., GEN2.2). Control and knockout cells would then be stimulated with a TLR7 agonist (e.g., R848) to mimic viral infection. The functional consequences would be assessed by measuring the transcription of key antiviral genes (*IFNA1*, *IFNB1*, *ISG15*) via RNA-seq and RT-qPCR, and the secretion of interferon-alpha protein into the supernatant by ELISA. A significant reduction in interferon production in the knockout cells would confirm that [MED26](/details-gene/9441) is critical for this specific pDC effector function. **Therapeutic Potential:** As a core component of the general transcriptional machinery, systemic inhibition of [MED26](/details-gene/9441) would likely be highly toxic. However, its potential as a therapeutic target lies in disrupting specific protein-protein interactions. If [MED26](/details-gene/9441) proves to be a crucial interaction hub for pathological transcription factors in diseases like cancer or autoimmune disorders, developing small molecules or peptidomimetics that block these specific interactions, while leaving its general function intact, could be a viable therapeutic strategy. This would represent a targeted inhibition approach aimed at modulating aberrant gene expression programs rather than shutting down transcription globally.

Genular Protein ID: 1895312999

Symbol: MED26_HUMAN

Name: Mediator of RNA polymerase II transcription subunit 26

UniProtKB Accession Codes:

O95402 A1A4S3 Q0VGB6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DNASU 1 DisGeNET 1 EMBL 3 EMDB 6 Ensembl 2 ExpressionAtlas 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 8 PDBsum 8 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 4 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9989412

Title: The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1.

PubMed ID: 9989412

DOI: 10.1038/17141

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 10235267

Title: Composite co-activator ARC mediates chromatin-directed transcriptional activation.

PubMed ID: 10235267

DOI: 10.1038/19789

PubMed ID: 15175163

Title: A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology.

PubMed ID: 15175163

DOI: 10.1016/j.molcel.2004.05.006

PubMed ID: 15989967

Title: MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription.

PubMed ID: 15989967

DOI: 10.1016/j.molcel.2005.05.015

PubMed ID: 20111005

Title: Crosstalk between C/EBPbeta phosphorylation, arginine methylation, and SWI/SNF/Mediator implies an indexing transcription factor code.

PubMed ID: 20111005

DOI: 10.1038/emboj.2010.3

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 26861138

Title: 1H, 15N and 13C assignments of the N-terminal domain of the Mediator complex subunit MED26.

PubMed ID: 26861138

DOI: 10.1007/s12104-016-9673-z

Sequence Information:

  • Length: 600
  • Mass: 65446
  • Checksum: 4BEA264A3EB5A407
  • Sequence:
    • MTAAPASPQQ IRDRLLQAID PQSNIRNMVA VLEVISSLEK YPITKEALEE TRLGKLINDV 
RKKTKNEELA KRAKKLLRSW QKLIEPAHQH EAALRGLAGA TGSANGGAHN CRPEVGAAGP 
PRSIHDLKSR NDLQRLPGQR LDRLGSRKRR GDQRDLGHPG PPPKVSKASH DPLVPNSSPL 
PTNGISGSPE SFASSLDGSG HAGPEGSRLE RDENDKHSGK IPVNAVRPHT SSPGLGKPPG 
PCLQPKASVL QQLDRVDETP GPPHPKGPPR CSFSPRNSRH EGSFARQQSL YAPKGSVPSP 
SPRPQALDAT QVPSPLPLAQ PSTPPVRRLE LLPSAESPVC WLEQPESHQR LAGPGCKAGL 
SPAEPLLSRA GFSPDSSKAD SDAASSGGSD SKKKKRYRPR DYTVNLDGQV AEAGVKPVRL 
KERKLTFDPM TRQIKPLTQK EPVRADSPVH MEQQSRTELD KQEAKASLQS PFEQTNWKEL 
SRNEIIQSYL SRQSSLLSSS GAQTPGAHHF MSEYLKQEES TRQGARQLHV LVPQSPPTDL 
PGLTREVTQD DLDRIQASQW PGVNGCQDTQ GNWYDWTQCI SLDPHGDDGR LNILPYVCLD