PROSITE documentation PDOC00550

Bromodomain signature and profile

The bromodomain [1,2,3] is a conserved region of about 70 amino acids found in the following proteins:

• Higher eukaryotes transcription initiation factor TFIID 250 Kd subunit (TBP-associated factor p250) (gene CCG1). P250 associated with the TFIID TATA-box binding protein and seems essential for progression of the G1 phase of the cell cycle.
• Human RING3, a protein of unknown function encoded in the MHC class II locus.
• Mammalian CREB-binding protein (CBP), which mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein.
• Drosophila female sterile homeotic protein (gene fsh), required maternally for proper expression of other homeotic genes involved in pattern formation, such as Ubx.
• Drosophila brahma protein (gene brm), a protein required for the activation of multiple homeotic genes.
• Mammalian homologs of brahma. In human, three brahma-like proteins are known: SNF2a(hBRM), SNF2b, and BRG1.
• Human BS69, a protein that binds to adenovirus E1A and inhibits E1A transactivation
• Human peregrin (or Br140).
• Yeast BDF1 [3], a transcription factor involved in the expression of a broad class of genes including snRNAs.
• Yeast GCN5, a general transcriptional activator operating in concert with certain other DNA-binding transcriptional activators, such as GCN4, HAP2/3/4 or ADA2.
• Yeast NPS1/STH1, involved in G(2) phase control in mitosis.
• Yeast SNF2/SWI2, which is part of a complex with the SNF5, SNF6, SWI3 and ADR6/SWI1 proteins. This SWI-complex is involved in transcriptional activation.
• Yeast SPT7, a transcriptional activator of Ty elements and possibly other genes.
• Caenorhabditis elegans protein cbp-1.
• Yeast hypothetical protein YGR056w.
• Yeast hypothetical protein YKR008w.
• Yeast hypothetical protein L9638.1.

Some proteins contain a region which, while similar to some extent to a classical bromodomain, diverges from it by either lacking part of the domain or because of an insertion. These proteins are:

• Mammalian protein HRX (also known as All-1 or MLL), a protein involved in translocations leading to acute leukemias and which possibly acts as a transcriptional regulatory factor. HRX contains a region similar to the C- terminal half of the bromodomain.
• Caenorhabditis elegans hypothetical protein ZK783.4. The bromodomain of this protein has a 23 amino-acid insertion.
• Yeast protein YTA7. This protein contains a region with significant similarity to the C-terminal half of the bromodomain. As it is a member of the AAA family (see <PDOC00572>) it is also in a functionally different context.

The above proteins generally contain a single bromodomain, but some of them contain two copies, this is the case of BDF1, CCG1, fsh, RING3, YKR008w and L9638.1.

The exact function of this domain is not yet known but it is thought to be involved in protein-protein interactions and it may be important for the assembly or activity of multicomponent complexes involved in transcriptional activation.

The consensus pattern that we have developed spans a major part of the bromodomain; a more sensitive detection is available through the use of a profile which spans the whole domain.