InterPro domain: IPR017923

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 [ 1 ].

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 [ 2 , 3 ], 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.
• IWS1, which is thought to function in both transcription initiation and elongation.

1. A sequence motif conserved in diverse nuclear proteins identifies a protein interaction domain utilised for nuclear targeting by human TFIIS. Nucleic Acids Res. 34, 2219-29
2. Structure of a conserved domain common to the transcription factors TFIIS, elongin A, and CRSP70. J. Biol. Chem. 275, 31266-8