RBBP5

RBBP5 (retinoblastoma-binding protein 5) is a protein encoded by the RBBP5 gene in humans. It is a component of conserved histone H3 lysine 4 (H3K4) methyltransferase complexes, commonly referred to as COMPASS-like complexes in mammals. RBBP5 functions as part of the core module that includes ASH2L, WDR5, DPY30, and members of the KMT2 family (KMT2A/MLL1 and KMT2B/MLL2), facilitating trimethylation of H3K4, a histone mark associated with transcriptional activation.

In biochemical terms, RBBP5 contributes to the assembly and stability of the complex and stimulates methyltransferase activity, enabling efficient H3K4 methylation across targeted genomic loci. The protein is predicted to contain WD40 repeats that form a beta-propeller structure, enabling protein–protein interactions within the complex.

RBBP5 is broadly expressed in human tissues and is required for normal development in model systems. In cells, loss or reduction of RBBP5 leads to decreased H3K4 methylation and altered gene expression patterns, underscoring its role in epigenetic regulation of transcription.

Clinically, dysregulation of H3K4 methylation pathways, including components of COMPASS-like complexes, has been implicated in cancer and developmental disorders. While specific therapeutic implications for RBBP5 are an active area of research, the protein remains a conserved and essential part of the epigenetic machinery governing gene expression.