Table 3.
Mammalian SET-domain protein methyltransferases that have been shown to modify non-histone substrates
| Protein | SET-domain family [4] |
Substrate and methylation position (from the mature N- terminus unless otherwise indicated) |
References |
|---|---|---|---|
|
Enzyme(s) that methylate histones and non-histone substrates |
|||
| EZH2 (KMT6) | Class I - EZ | histone H3 Lys-27 retinoic acid-related orphan nuclear receptor α (RORα) Lys-38 transcription factor GATA4 Lys-299 |
[49,50] [49] [50] |
| SETD1A (KMT2F) | Class II - SET2 | histone H3 Lys-4 heat-shock protein 70 (HSP70; HSPA1A) Lys-560 (dimethyl) |
[51] [52] |
| EHMT1 (KMT1D)(GLP)/ EHMT2 (KMT1C)(G9A) |
Class V - Suvar-3-9 - histone H3 Lys-9 |
histone H1 histone H3 Lys-9 (mono and dimethyl) histone H3 Lys-27 chromodomain Y-like protein (CDYL1) Lys- 135 (mono, di, and trimethyl) widely-interspaced zinc finger-containing protein (WIZ) Lys- 1162 (di and trimethyl) apoptotic chromatin condensation inducer in the nucleus (ACINUS) Lys-654 (di and trimethyl) p53 transcription factor Lys-373 (dimethyl) MyoD transcription factor Lys-104 |
[53] [53] [53] [54] [54] [54] [55] [56] |
| SETDB1 | Class V - Suvar-3–9 - histone H3 Lys-9 |
histone H3 Lys-9 HIV1 Tat transcriptional activator Lys-50, Lys- 51 |
[57] |
| SMYD3 | Class VI – SMYD | histone H4 Lys-5 Vascular endothelial growth factor receptor 1 tyrosine kinase Lys- 831 |
[58] [59] |
| SETD6 | Class VII - SET6 | histone H2AZ Lys-7 RelA subunit of NF- kappa B transcription factor Lys-310 (monomethyl) serine/threonine protein kinase PLK1 serine/threonine protein kinase PAK4 |
[60] [61] [61] [61] |
| SETD8 (SET8) (KMT5A)(PrR/SET7) |
PR/SET | histone H4 Lys-20 (monomethyl) p53 transcription factor Lys-382 |
[62] [62,63] |
| SETD7 (KMT7) (SET7/9)(SET7)(SET9) |
SET7 | A wide variety of substrates including: histone H2A histone H2B DNMT1 DNA methyltransferase Lys-142 estrogen receptor-α p53 transcription factor Lys-372 TFIID protein TAF10 Lys-189 FOXO3 Lys-270 |
[37,64,65] |
|
Enzymes that methylate only non- histone substrates |
|||
| SMYD2 (KMT3C) | Class VI - SMYD | monomethylation at: p53 Lys-370 Hsp90 Lys-209, Lys- 615 RB1 retinoblastoma- associated protein Lys-850 |
[66] [67] [68] |