Function: Component of the Mediator complex, 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. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Required for RARA/RXRA-mediated transcription. Ref.2 Ref.3 Ref.13
Subunit structure: Component of the Mediator complex, which is composed of 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 MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with CREBBP. Interacts with ESR1, GR, RARA, RXRA and THRB in a ligand-dependent fashion. Binds the Herpes simplex virus activator VP16. Ref.2 Ref.3 Ref.11 Ref.12 Ref.13
Subcellular location: Nucleus Ref.2.
Tissue specificity: Ubiquitously expressed. Highest levels in brain, heart, kidney, peripheral leukocytes, placenta, skeletal muscle and spleen. Ref.2 Ref.3
Involvement in disease: Charcot-Marie-Tooth disease 2B2 (CMT2B2) [MIM:605589]: A recessive axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15
Sequence similarities: Belongs to the Mediator complex subunit 25 family.
Sequence caution: The sequence AAG15589.1 differs from that shown. Reason: Erroneous initiation. The sequence CAB66680.1 differs from that shown. Reason: Frameshift at position 567.
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