SETD2 — SET domain containing 2, histone lysine methyltransferase
SETD2 belongs to a gene co-expression module in 5 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
SETD2's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| CD19⁺ B cells | Chromatin & genome maintenance DNA/chromatin regulation | ARID1B, ASH1L, ATM, ATRX, BOD1L1, DDX17, KANSL1, MARF1 +8 more | View in SCUBA |
| CD4⁺ T cells | TCR signaling activation TCR/AP1/NFKb pathway | CNST, CORO1B, DAPP1, ECI1, FAAH2, FCMR, GPCPD1, KLHL24 +8 more | View in SCUBA |
| Gamma-delta T cells | Transcription-RNA Coupling DNA/chromatin regulation | AKNA, AP1G1, BTAF1, BZW1, CRNKL1, DDX6, DNTTIP2, DYNC1H1 +26 more | |
| Macrophages | Chromatin Epigenetic Regulation Housekeeping | ABHD17B, ANKH, ARHGAP21, CCNH, CTTNBP2NL, DMXL1, EEIG2, ELF2 +21 more | View in SCUBA |
| Mucosal-associated invariant T cell | Epigenetic Maintenance DNA/chromatin regulation | ATAD2B, ATXN10, DENND6A, DGLUCY, DMTF1, FYCO1, GALK2, HDLBP +13 more |
About the gene
| Synonyms | FLJ23184, HIF-1, HYPB, KIAA1732, KMT3A |
|---|---|
| Chromosome | 3: 47016428-47164113 |
| Predicted location | Intracellular |
| Essential gene | Yes |
| Protein class | Cancer-related genes, Disease related genes, Enzymes, Essential proteins, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins |
| Molecular function | Activator, Chromatin regulator, Developmental protein, Methyltransferase, Transferase |
| Biological process | Antiviral defense, Differentiation, DNA damage, DNA repair, Host-virus interaction, Immunity, Innate immunity, Transcription, Transcription regulation |
Function
Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate. It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro. Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (By similarity). Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A. Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction. Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR). Acts as a tumor suppressor. H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A. H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase. Required during angiogenesis (By similarity). Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (By similarity). In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1. Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha- TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling. Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription. (Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.