L3MBTL histone methyl-lysine binding protein 3 (L3MBTL3)

L3MBTL3 (L3MBTL histone methyl-lysine binding protein 3) is a chromatin-interacting protein and member of the malignant brain tumor (MBT) family, characterized by the presence of MBT and SAM domains. It functions as a histone methyl-lysine reader, recognizing mono- and dimethylated lysine residues on histone tails through its MBT domains, and binds methylated lysines on both histone and non-histone proteins. L3MBTL3 plays a role in the repression of gene expression by compacting chromatin, recruiting demethylases (e.g., KDM1A), and mediating ubiquitin-dependent degradation of methylated proteins, acting as an adaptor for ubiquitin ligase complexes. It is essential in embryonic development, especially hematopoiesis, and has been linked to developmental disorders and cancers, with deletion or mutation observed in medulloblastoma. Selective small molecule inhibitors like UNC1215 provide research tools to dissect L3MBTL3 function and mechanisms of histone methylation readout.

Other names

Lethal(3)malignant brain tumor-like protein 3KIAA1798MBT1H-l(3)mbt-like protein 3L(3)mbt-like protein 3MBT-1histone methyl-lysine binding proteinl(3)mbt-like 3

Small molecule inhibitors (e.g., UNC1215) occupy the methyl-lysine binding pocket, preventing L3MBTL3 from binding to histone tails and altering chromatin-related functions