MEDIATOR COMPLEX SUBUNIT 29; MED29

Alternative titles; symbols

• INTERSEX, DROSOPHILA, HOMOLOG OF
• INTERSEX-LIKE; IXL

HGNC Approved Gene Symbol: MED29

Cytogenetic location: 19q13.2 Genomic coordinates (GRCh38): 19:39,391,377-39,400,640 (from NCBI)

▼ Description

MED29 is a subunit of the Mediator complex, a multiprotein coactivator of RNA transcription that interacts with DNA-bound transcriptional activators, RNA polymerase II (see 180660), and general initiation factors (Sato et al., 2003).

▼ Cloning and Expression

By sequencing peptide fragments from a protein that copurified with the HeLa cell Mediator complex, followed by database analysis, Sato et al. (2003) identified MED29, which they called Intersex.

By searching a human EST database for sequences similar to Drosophila Intersex, followed by PCR of a fetal heart cDNA library and 5-prime and 3-prime RACE, Wang et al. (2004) cloned MED29, which they called IXL. The deduced 221-amino acid protein has a calculated molecular mass of 23.5 kD. It contains a PxxP motif for binding SRC (190090) homology-3 (SH3) domains. IXL is highly conserved across a wide range of species, and it shares 92% amino acid identity with mouse Ixl and 36% identity with Drosophila Intersex. Northern blot analysis detected a 3.6-kb transcript expressed at variable levels in all adult and fetal human tissues examined. Fluorescence-tagged IXL localized predominantly to the nucleus, but also to the cytoplasm, of transfected COS-7 cells.

▼ Gene Function

Using coimmunoprecipitation analysis and protein pull-down assays, Sato et al. (2003) confirmed that MED29 is a Mediator subunit. Coexpression of epitope-tagged proteins revealed that MED29 interacted most strongly with the Mediator subunit TRFP (MED20; 612915), and TRFP appeared the bridge an interaction between MED29 and p28b (MED18; 612384).

Wang et al. (2004) showed that IXL suppressed transcription of a reporter gene upon cotransfection in COS-7 cells. IXL specifically suppressed the transcriptional activities of the FOS (164810) serum response element (SRE) and AP1 (see 165160), suggesting that IXL is a transcriptional suppressor within MAP kinase (see MAPK1; 176948) signaling pathways.

▼ Gene Structure

Wang et al. (2004) determined that the MED29 gene contains 4 exons and spans about 9.3 kb.

▼ Mapping

By genomic sequence analysis, Wang et al. (2004) mapped the MED29 gene to chromosome 19q13.2.