Pathways & interactions
SWIB/MDM2 domain superfamily (IPR036885)
Short name: SWIB_MDM2_dom_sf
- SWIB/MDM2 domain (IPR003121)
- Ubiquitin-protein ligase E3 MDM2 (IPR015459)
- p53 negative regulator Mdm2/Mdm4 (IPR016495)
- SWIB domain (IPR019835)
- E3 ubiquitin-protein ligase Mdm2 (IPR028340)
- SWI/SNF complex subunit BAF60B (IPR030090)
- SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1 (IPR038041)
- SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 3 (IPR038043)
The SWI/SNF family of complexes, which are conserved from yeast to humans, are ATP-dependent chromatin-remodelling proteins that facilitate transcription activation [PMID: 11147808]. The mammalian complexes are made up of 9-12 proteins called BAFs (BRG1-associated factors). The BAF60 family have at least three members: BAF60a, which is ubiquitous, BAF60b and BAF60c, which are expressed in muscle and pancreatic tissues, respectively. BAF60b is present in alternative forms of the SWI/SNF complex, including complex B (SWIB), which lacks BAF60a. The SWIB domain is a conserved region found within the BAF60b proteins [PMID: 12016060], and can be found fused to the C terminus of DNA topoisomerase in Chlamydia.
MDM2 is an oncoprotein that acts as a cellular inhibitor of the p53 tumour suppressor by binding to the transactivation domain of p53 and suppressing its ability to activate transcription [PMID: 8875929]. p53 acts in response to DNA damage, inducing cell cycle arrest and apoptosis. Inactivation of p53 is a common occurrence in neoplastic transformations. The core of MDM2 folds into an open bundle of four helices, which is capped by two small 3-stranded beta-sheets. It consists of a duplication of two structural repeats. MDM2 has a deep hydrophobic cleft on which the p53 alpha-helix binds; p53 residues involved in transactivation are buried deep within the cleft of MDM2, thereby concealing the p53 transactivation domain.
The SWIB and MDM2 domains are homologous and share a common fold. The core of this domain is composed of four helices arranged in an open bundle, capped by two small 3-stranded beta-sheets.