histone-lysine N-methyltransferase 2D; lysine N-methyltransferase 2D; ALL1-related protein; myeloid/lymphoid or mixed-lineage leukemia protein 2 (KMT2D, ALR, MLL2, MLL4)
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Function
- histone methyltransferase
- methylates Lys-4 of histone H3
- histone H3 Lys-4 methylation represents a specific tag for epigenetic transcriptional activation
- plays a central role in beta-globin locus transcription regulation by being recruited by NFE2
- acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription
- phosphorylated upon DNA damage, probably by ATM or ATR
- component of the MLL2/MLL3 complex
- interacts with NFE2
- interacts with ESR1; interaction is direct
S-adenosyl-L-methionine + L-lysine-[histone] <-> S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]
Structure
- LXXLL motifs 5 & 5 are essential for the association with ESR1 nuclear receptor
- belongs to the histone-lysine methyltransferase family, TRX/MLL subfamily
- contains 1 FYR C-terminal domain
- contains 1 FYR N-terminal domain
- contains 5 PHD-type Zn+2 fingers
- contains 1 post-SET domain
- contains 4 RING-type Zn+2 fingers
- contains 1 SET domain
Compartment
- nucleus (probable)
Alternative splicing
- named isoforms=2
Expression
- expressed in most adult tissues, including a variety of hematoipoietic cells
- not expressed in liver
Pathology
- mutations in KMT2D are associated with Kabuki syndrome 1
Genetics
- gene mapped to a chromosomal region involved in duplications & translocations associated with cancer
Notes
- another protein KMT2B/MLL4, located on chromosome 19, was first named MLL2
- thus, KMT2B/MLL4 is often referred to as MLL2 & vice versa in the literature