TAF1

Transcription initiation factor TFIID subunit 1, also known as transcription initiation factor TFIID 250 kDa subunit (TAFII-250) or TBP-associated factor 250 kDa (p250), is a is_associated_with::protein that in humans is encoded by the TAF1 is_associated_with::gene.

Function
Initiation of transcription by is_associated_with::RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is the basal transcription factor TFIID, which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes the largest subunit of TFIID. This subunit binds to core promoter sequences encompassing the transcription start site. It also binds to activators and other transcriptional regulators, and these interactions affect the rate of transcription initiation. This subunit contains two independent is_associated_with::protein kinase domains at the N and C-terminals, but also possesses is_associated_with::acetyltransferase activity and can act as a is_associated_with::ubiquitin-activating/conjugating enzyme. Two transcripts encoding different isoforms have been identified for this gene.

Clinical significance
A mutation in TAF1 was identifed that contributes to a phenotype with severe intellectual disability (ID), a characteristic intergluteal crease, and very distinctive facial features, including a broad, upturned nose, sagging cheeks, downward sloping palpebral fissures, prominent periorbital ridges, deep-set eyes, relative hypertelorism, thin upper lip, a high-arched palate, prominent ears with thickened helices, and a pointed chin This is a non-synonymous change in TAF1 that results in an isoleucine (hydrophobic) to threonine (polar) change on the 1337th amino acid residue in the protein (NP_001273003.1). Two other mutations were reported in TAF1 in two families with intellectual disability, although further clinical details were not reported.

Interactions
TAF1 has been shown to interact with:


 * CSNK2A1,
 * CCND1,
 * is_associated_with::GTF2F1,
 * RB1,
 * is_associated_with::TAF7,
 * TBP,    and
 * is_associated_with::UBTF.