L3MBTL1
Developmental stage
In interphase cells, it is scattered throughout the nucleoplasm. In mitotic cells, it strongly associates with condensed chromosomes from the prophase to telophase.
Domain
The MBT repeat 2 specifically recognizes and binds monomethylated and dimethylated proteins. In contrast, it does not bind trimethylated proteins. The MBT repeat 1 does not bind methylated peptides but inserts a proline ring in a Pro-Ser-Ser/Thr sequence context.
Function
Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, therey acting as a 'reader' of a network of post-translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/H1-4 at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis.
Post-translational modifications
Ubiquitinated in a VCP/p97-dependent way following DNA damage, leading to its removal from DNA damage sites, promoting accessibility of H4K20me2 mark for DNA repair protein TP53BP1, which is then recruited to DNA damage sites.
Tissue Specificity
Widely expressed. Expression is reduced in colorectal cancer cell line SW480 and promyelocytic leukemia cell line HL-60.
Cellular localization
- Nucleus
- Excluded from the nucleolus. Does not colocalize with the PcG protein BMI1, suggesting that these two proteins do not belong to the same complex.
Alternative names
KIAA0681, L3MBT, L3MBTL, L3MBTL1, Lethal(3)malignant brain tumor-like protein 1, H-l(3)mbt, H-l(3)mbt protein, L(3)mbt-like, L(3)mbt protein homolog