Reactome | Formation of the RBBP5:ASH2L heterodimer

Formation of the RBBP5:ASH2L heterodimer

Stable Identifier

R-HSA-9675215

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Formation of the RBBP5:ASH2L heterodimer

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

RBBP5 and ASH2L interact and form a heterodimer (Cao et al. 2010, Li et al. 2016). RBBP5 is a WD40 family protein, whose WD40 repeat beta-propeller domain possesses a cluster of arginine residues on its surface. Based on structural studies using mouse Rbbp5, this arginine-rich WD40 repeat beta-propeller domain can directly interact with nucleic acids, thus facilitating the recruitment of KMT2 complexes to chromatin (Mittal et al. 2018).

The ASH2L subunit is important for the KMT2-mediated histone H3K4 trimethylation, and its stability depends on the interaction with WDR5 (Steward et al. 2006). The interaction between RBBP5 and ASH2L involves a cluster of acidic residues, known as the D/E box on RBBP5 and the SPRY (SPIa and ryanodine receptor) domain of ASH2L (Zhang et al. 2015). Phosphorylation of the evolutionarily conserved serine S350 in the D/E box of RBBP5 enhances its binding to the SPRY domain of ASH2L (Zhang et al. 2015). While phosphorylation of S350 has been reported in cells, the responsible kinase is unknown (Zhang et al. 2015).

Literature References

PubMed ID	Title	Journal	Year
26886794	Structural basis for activity regulation of MLL family methyltransferases Zhang, J, Tian, C, Han, J, Li, G, Li, D, Li, Y, Dou, Y, Cao, L, Hu, C, Chen, Y, Zhang, Y, Wang, Y, Shi, P, Wu, J, Lei, M, Chen, J, Liu, Z, Cao, F, Shuai, J, Li, S	Nature	2016
21124902	An Ash2L/RbBP5 heterodimer stimulates the MLL1 methyltransferase activity through coordinated substrate interactions with the MLL1 SET domain Lei, M, Basrur, V, Cierpicki, T, Cao, F, Dou, Y, Chen, Y, Liu, Y	PLoS ONE	2010
16892064	Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes Steward, MM, Bernstein, BE, O'Donovan, A, Shilatifard, A, Lee, JS, Wyatt, M	Nat Struct Mol Biol	2006
29897600	The structure of the RbBP5 β-propeller domain reveals a surface with potential nucleic acid binding sites Zhang, Y, Wilson, JR, Gamblin, SJ, Mittal, A, Hobor, F, Ramos, A, Martin, SR	Nucleic Acids Res	2018
25593305	A phosphorylation switch on RbBP5 regulates histone H3 Lys4 methylation Couture, JF, Brunzelle, JS, Skiniotis, G, Shilatifard, A, Zhang, P, Cramet, M, Tremblay, V, Chaturvedi, CP, Brand, M	Genes Dev	2015