Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3 (H3K4). Functions as a transcriptional regulator. Binds to the TERT promoter and represses telomerase expression. Plays a role in TGFB1-mediated inhibition of cell-proliferation, possibly regulating SMAD3 transcriptional activity. Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. Positively regulates HOXC8 and HOXC6 gene expression. May be involved in normal hematopoiesis through the activation of HOXA9 expression. May be involved in DNA repair. Component of MLL-containing complexes (named MLL, ASCOM, MLL2/MLL3 or MLL3/MLL4 complex): at least composed ASH2L, RBBP5, DPY30, WDR5, one or several histone methyltransferases (MLL, MLL2, MLL3 and/or MLL4), and the facultative components MEN1, HCFC1, HCFC2, NCOA6, KDM6A, PAXIP1/PTIP and C16orf53/PA1. Interacts with POLR2A phosphorylated at 'Ser-5', but not with the unphosphorylated, nor 'Ser-2' phosphorylated POLR2A forms. Interacts with FANCD2 and DBF4. Interacts with JUND. Interacts with SMAD3, but not with SMAD2, nor SMAD4. Directly interacts with NFKB1, NFKB2 and RELA. Ubiquitous. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Transcription, coactivator/corepressor
Molecular Function: chromatin binding; double-stranded DNA binding; four-way junction DNA binding; histone-lysine N-methyltransferase activity; protein binding; protein binding, bridging; protein N-terminus binding; Y-form DNA binding
Biological Process: brain development; decidualization; DNA repair; gene expression; MAPKKK cascade; mitotic cell cycle; negative regulation of cell cycle; negative regulation of cell proliferation; negative regulation of cyclin-dependent protein kinase activity; negative regulation of epithelial cell proliferation; negative regulation of JNK cascade; negative regulation of osteoblast differentiation; negative regulation of protein amino acid phosphorylation; negative regulation of telomerase activity; negative regulation of transcription factor activity; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; osteoblast development; positive regulation of protein binding; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transforming growth factor beta receptor signaling pathway; regulation of activin receptor signaling pathway; response to DNA damage stimulus; response to gamma radiation; response to UV; small GTPase mediated signal transduction; transcription initiation from RNA polymerase II promoter; transcription, DNA-dependent; transforming growth factor beta receptor signaling pathway
LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.