Mediator is a large complex of up to 33 proteins that is conserved from plants to fungi to humans - the number and representation of individual subunits varying with species PMID:14983011,PMID:17560376. It is arranged into four different sections, a core, a head, a tail and a kinase-active part, and the number of subunits within each of these is what varies with species. Overall, Mediator regulates the transcriptional activity of RNA polymerase II, but it would appear that each of the four different sections has a slightly different function PMID:18381891. The overall function of the full-length Med25 is efficiently to coordinate the transcriptional activation of RAR/RXR (retinoic acid receptor/retinoic X receptor) in higher eukaryotic cells. Human Med25 consists of several domains with different binding properties, the N-terminal, VWA domain, an SD1 - synapsin 1 - domain from residues 229-381, a PTOV(B) or ACID domain from 395-545, an SD2 domain from residues 564-645 and a C-terminal NR box-containing domain (646-650) from 646-747.

This superfamily includes the ACID domain (activator-interacting domain). Unlike other known activator targets, ACID forms a seven-stranded beta-barrel framed by three helices. The ACID domain appears to impose a critical control on transcription activation by VP16 in mammalian cells, uncovering a novel molecular activation pathway of VP16 through transcriptional complexes containing the MED25 subunit.

INTERPRO:IPR021394, PFAM:PF11232,DOI:10.1007/s10969-011-9115-1,DOI:10.1016/j.jsb.2010.10.011,DOI:10.1038/nsmb.1999,DOI:10.1038/nsmb.1997