Homologous Superfamily

TFIIS/LEDGF domain superfamily (IPR035441)

Short name: TFIIS/LEDGF_dom_sf

Description

This superfamily is composed of the Transcription factor IIS (TFIIS) and the Lens epithelium-derived growth factor (LEDGF) domains.

Transcription factor IIS (TFIIS) is a transcription elongation factor that increases the overall transcription rate of RNA polymerase II by reactivating transcription elongation complexes that have arrested transcription. The three structural domains of TFIIS are conserved from yeast to human. The 80 or so N-terminal residues form a protein interaction domain containing a conserved motif, which has been called the LW motif because of the invariant leucine and tryptophan residues it contains. This N-terminal domain is not required for transcriptional activity, and while a similar sequence has been identified in other transcription factors, and proteins that are predominantly nuclear localized [PMID: 10811649, PMID: 16648364], the domain is also found in proteins not directly involved in transcription. This domain is found in (amongst others):

  • MED26 (also known as CRSP70 and ARC70), a subunit of the Mediator complex, which is required for the activity of the enhancer-binding protein Sp1.
  • Elongin A, a subunit of a transcription elongation factor previously known as SIII. It increases the rate of transcription by suppressing transient pausing of the elongation complex.
  • PPP1R10, a nuclear regulatory subunit of protein phosphatase 1 that was previously known as p99, FB19 or PNUTS.
  • PIBP, a small hypothetical protein that could be a phosphoinositide binding protein.
  • IWS1, which is thought to function in both transcription initiation and elongation.

The TFIIS N-terminal domain is a compact four-helix bundle. The hydrophobic core residues of helices 2, 3, and 4 are well conserved among TFIIS domains, although helix 1 is less conserved [PMID: 16648364].

Lens epithelium-derived growth factor (LEDGF), also known as transcriptional co-activator p75, is a chromatin-associated protein that protects cells from stress-induced apoptosis. It is the binding partner of HIV-1 integrase in human cells [PMID: 15371438]. The integrase binding domain (IBD) of LEDGF is a compact right-handed bundle composed of five alpha-helices. The residues essential for the interaction with the integrase are present in the inter-helical loop regions of the bundle structure. The integrase binding domain is not unique to LEDGF, as a second human protein, hepatoma-derived growth factor-related protein 2 (HRP2), contains a homologous sequence [PMID: 15371438].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
GENE3D
SUPERFAMILY