Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17500065, PubMed:25561738). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732)

Component of the MLL2 complex (also named ASCOM complex), at least composed of catalytic subunit KMT2D/MLL2, ASH2L, RBBP5, WDR5, NCOA6, DPY30, KDM6A, PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin (PubMed:12482968, PubMed:16603732, PubMed:17021013, PubMed:17500065, PubMed:17761849, PubMed:17851529, PubMed:23508102). Forms a core complex with the evolutionary conserved subcomplex WRAD composed of WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits; WRAD differentially stimulates the methyltransferase activity (PubMed:25561738). Interacts with ESR1; interaction is direct (PubMed:16603732).

Interacts (via WIN motif) with WDR5 (PubMed:22266653, PubMed:22665483)

Expressed in most adult tissues, including a variety of hematoipoietic cells, with the exception of the liver

LXXLL motifs 5 and 6 are essential for the association with ESR1 nuclear receptor

• Kabuki syndrome 1 (KABUK1)

  An autosomal dominant, congenital syndrome characterized by intellectual disability and additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids, a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy.

• Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome (BCAHH)

  An autosomal dominant disorder characterized by choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, delayed or absent pubertal development, and thyroid abnormalities. Additional features may include developmental delay, growth failure and short stature.