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: Y-form DNA binding; protein binding, bridging; protein binding; four-way junction DNA binding; double-stranded DNA binding; protein N-terminus binding; chromatin binding; histone-lysine N-methyltransferase activity
Biological Process: negative regulation of JNK cascade; positive regulation of protein binding; decidualization; negative regulation of transcription from RNA polymerase II promoter; negative regulation of cell cycle; negative regulation of cell proliferation; negative regulation of protein amino acid phosphorylation; small GTPase mediated signal transduction; transforming growth factor beta receptor signaling pathway; response to gamma radiation; negative regulation of osteoblast differentiation; response to UV; negative regulation of epithelial cell proliferation; transcription initiation from RNA polymerase II promoter; transcription, DNA-dependent; negative regulation of transcription factor activity; positive regulation of transforming growth factor beta receptor signaling pathway; negative regulation of cyclin-dependent protein kinase activity; MAPKKK cascade; DNA repair; regulation of activin receptor signaling pathway; osteoblast development; negative regulation of telomerase activity; positive regulation of transcription from RNA polymerase II promoter; gene expression; mitotic cell cycle; brain development; negative regulation of transcription, DNA-dependent; response to DNA damage stimulus
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.