Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription (PubMed:23629655, PubMed:24130829, PubMed:23798402). Chromatin interaction is mediated via the binding to tri-methylated histone H3 at 'Lys-4' (H3K4me3) (PubMed:24130829, PubMed:23798402). Key regulator of hematopoiesis involved in terminal myeloid differentiation and in the regulation of hematopoietic stem cell (HSCs) self-renewal by a mechanism that involves DNA methylation (By similarity). Also acts as an important cell cycle regulator, participating in cell cycle regulatory network machinery at multiple cell cycle stages including G1/S transition, S phase progression and mitotic entry (PubMed:14718661, PubMed:18573682, PubMed:19264965, PubMed:23629655). Recruited to E2F1 responsive promoters by HCFC1 where it stimulates tri-methylation of histone H3 at 'Lys-4' and transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). During myoblast differentiation, required to suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells (By similarity). Cellular ligand for NCR2/NKp44, may play a role as a danger signal in cytotoxicity and NK-cell-mediated innate immunity. Component of a complex composed of KMT2E (isoform 3), OGT and USP7; the complex stabilizes KMT2E, preventing KMT2E ubiquitination and proteosomal-mediated degradation (PubMed:26678539). Isoform 3 interacts (via N-terminus) with OGT (via TRP repeats) (PubMed:26678539, PubMed:23629655). Isoform 3 interacts with deubiquitinating enzyme USP7 (via MATH domain) (PubMed:26678539). Isoform 3 interacts (via HBM motif) with HCFC1 (via Kelch domain) (PubMed:23629655). Isoform 3 interacts with E2F1; the interaction is probably indirect and is mediated via HCFC1 (PubMed:23629655). Absent from the nucleolus (PubMed:14718661). Localizes to chromosome during interphase and to centrosomes during mitosis (PubMed:23798402). Dissociation from mitotic chromosome is likely due to histone H3 phosphorylation on 'Thr-3' and 'Thr-6' (PubMed:23798402). Absent from the nucleolus (PubMed:23629655). Localizes to chromosome during interphase and to nucleus speckle during mitosis (PubMed:23798402). Dissociation from mitotic chromosome is likely due to histone H3 phosphorylation on 'Thr-3' and 'Thr-6' (PubMed:23798402). Widely expressed in both adult and fetal tissues (PubMed:12101424, PubMed:23958951). Highest levels of expression observed in fetal thymus and kidney and in adult hematopoietic tissues, jejunum and cerebellum (PubMed:12101424, PubMed:23958951). Isoform NKp44L: Not detected on circulating cells from healthy individuals, but is expressed on a large panel of tumor and transformed cells (PubMed:23958951). The PHD-type domain binds specifically histone H3 tri-methylated at 'Lys-4' (H3K4me3), thus promoting binding to chromatin. The SET domain does not bind the methyl group donor S-adenosyl-L-methionine and histone 3 H3K4 peptide as a large loop prevents the docking of the 'Lys-4' side chain. The C-terminus domain is responsible for the localization to the centrosome during mitosis. Ubiquitinated. Deubiquitinated by USP7. O-glycosylated at Ser-435 and Thr-440 in the SET domain by OGT which probably prevents KMT2E proteasomal-mediated degradation. The disease is caused by variants affecting the gene represented in this entry. Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily. Isoform 3 was originally thought to display histone methyltransferase activity only following O-glycosylation at Thr-440 (PubMed:19377461). However, the corresponding article has been retracted (PubMed:24336203). Does not exhibit histone methyltransferase towards histone H3 in vitro (PubMed:19264965, PubMed:27812132). The isolated catalytic SET domain lacks binding activity towards cofactor S-adenosyl-L-methionine; instead of the highly conserved XGXG, Y and NH motifs, KMT2E displays NKKI (Asn-339-Ile-342), F (Phe-381) and RR (Arg-408-Arg-409) motifs (PubMed:27812132). Also lacks binding activity towards histone H3 due to a poor conservation of the key residues involved in the binding and the presence of large loop which prevents the docking of the H3 'Lys-4' side chain (PubMed:27812132). Contaminating sequence. Potential poly-A sequence starting in position 492. Contaminating sequence. Potential poly-A sequence starting in position 227. Contaminating sequence. Potential poly-A sequence starting in position 227. Contaminating sequence. Potential poly-A sequence starting in position 492.