Histone-lysine N-methyltransferase SETD7 (SETD7) (SETD7)

Histone-lysine N-methyltransferase SETD7 (also known as SET7/9) is a critical epigenetic regulator that catalyzes the monomethylation of lysine residues on both histone and non-histone proteins [1.1.1, 1.2.5]. Its primary histone substrate is lysine 4 of histone H3 (H3K4me1), a modification typically associated with transcriptional activation and chromatin remodeling [1.1.3, 1.2.4]. Beyond its role in chromatin modification, SETD7 methylates a wide variety of non-histone proteins, including p53, estrogen receptor alpha (ERα), DNMT1, and STAT3, thereby modulating their stability, activity, and cellular localization [1.1.1, 1.4.2]. This broad substrate range allows SETD7 to influence essential biological processes such as cell cycle progression, apoptosis, DNA damage response, and inflammatory signaling [1.2.4, 1.3.1]. In clinical contexts, SETD7 is frequently dysregulated in various cancers, where it often promotes tumor growth and metastasis, although its role can be paradoxically suppressive depending on the specific cellular environment [1.1.1, 1.1.2]. Due to its involvement in oncogenesis, diabetes, and inflammation, SETD7 has emerged as a promising therapeutic target, with selective inhibitors like (R)-PFI-2 and repurposed drugs like cyproheptadine being explored for their potential to modulate its activity in disease states [1.2.4, 1.3.1].

Other names

SETD7KMT7SET7SET7/9SET9KIAA1717SET domain-containing protein 7Lysine N-methyltransferase 7Histone H3-K4 methyltransferase SETD7

Inhibition of protein lysine N-methyltransferase activity by competing with the histone substrate or occupying the S-adenosylmethionine (SAM) binding pocket [1.2.4, 1.3.1].