histone-lysine N-methyltransferase 2D; lysine N-methyltransferase 2D; ALL1-related protein; myeloid/lymphoid or mixed-lineage leukemia protein 2 (KMT2D, ALR, MLL2, MLL4)

Function: - histone methyltransferase - methylates Lys-4 of histone H3 - histone H3 Lys-4 methylation represents a specific tag for epigenetic transcriptional activation - plays a central role in beta-globin locus transcription regulation by being recruited by NFE2 - acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription - phosphorylated upon DNA damage, probably by ATM or ATR - component of the MLL2/MLL3 complex - interacts with NFE2 - interacts with ESR1; interaction is direct S-adenosyl-L-methionine + L-lysine-[histone] S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone] Structure: - LXXLL motifs 5 & 5 are essential for the association with ESR1 nuclear receptor - belongs to the histone-lysine methyltransferase family, TRX/MLL subfamily - contains 1 FYR C-terminal domain - contains 1 FYR N-terminal domain - contains 5 PHD-type Zn⁺² fingers - contains 1 post-SET domain - contains 4 RING-type Zn⁺² fingers - contains 1 SET domain Compartment: - nucleus (probable) Alternative splicing: - named isoforms=2 Expression: - expressed in most adult tissues, including a variety of hematoipoietic cells - not expressed in liver Pathology: - mutations in KMT2D are associated with Kabuki syndrome 1 Genetics: - gene mapped to a chromosomal region involved in duplications & translocations associated with cancer Note: - another protein KMT2B/MLL4, located on chromosome 19, was first named MLL2 - thus, KMT2B/MLL4 is often referred to as MLL2 & vice versa in the literature

General

nuclear protein N-methyltransferase phosphoprotein ring finger protein

Properties

SIZE: entity length = 5537 aa MW = 593 kD COMPARTMENT: cell nucleus MOTIF: Ser phosphorylation site {S27} Zn finger PHD-type NAME: Zn finger PHD-type SITE: 226-276 EFFECTOR-BOUND: Zn+2 cysteine-rich region {229-326} MOTIF: RING-finger {229-274} EFFECTOR-BOUND: Zn+2 FOR-BINDING-OF: DNA motif Zn finger PHD-type NAME: Zn finger PHD-type SITE: 273-323 EFFECTOR-BOUND: Zn+2 RING-finger {276-321} EFFECTOR-BOUND: Zn+2 FOR-BINDING-OF: DNA motif proline-rich region SITE: 374-1197 MOTIF: proline residue (SEVERAL) 15 X 5 AA repeats of S/P-P-P-E/P-E/A {439-668} consensus repeat {442-446} consensus repeat {460-464} consensus repeat {469-473} consensus repeat {496-500} consensus repeat {504-508} consensus repeat {521-525} consensus repeat {555-559} consensus repeat {564-568} consensus repeat {573-577} consensus repeat {582-586} consensus repeat {609-613} consensus repeat {618-622} consensus repeat {627-631} consensus repeat {645-649} consensus repeat {663-667} arginine-rich region {1290-1328} MOTIF: arginine residue (SEVERAL) glutamate-rich region {1351-1355} MOTIF: glutamate residue (SEVERAL) Zn finger PHD-type NAME: Zn finger PHD-type SITE: 1377-1430 EFFECTOR-BOUND: Zn+2 cysteine-rich region {1397-1510} MOTIF: Zn finger PHD-type NAME: Zn finger PHD-type SITE: 1427-1477 EFFECTOR-BOUND: Zn+2 Zn finger PHD-type NAME: Zn finger PHD-type SITE: 1504-1559 EFFECTOR-BOUND: Zn+2 MOTIF: RING-finger {1507-1557} EFFECTOR-BOUND: Zn+2 FOR-BINDING-OF: DNA motif Ser phosphorylation site {S1606} Ser phosphorylation site {S1671} proline-rich region SITE: 2107-2626 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S2274} Ser phosphorylation site {S2309} Ser phosphorylation site {S2311} proline-rich region SITE: 2385-2392 MOTIF: proline residue (SEVERAL) coiled coil {2669-2707} MOTIF: LXXLL motif 1 {2686-2690} alanine-rich region {2707-2713} MOTIF: alanine residue (SEVERAL) glutamine-rich region {2811-2822} MOTIF: glutamine residue (SEVERAL) proline-rich region SITE: 2862-2978 MOTIF: proline residue (SEVERAL) LXXLL motif 2 {3038-3042} Ser phosphorylation site {S3130} Thr phosphorylation site {T3197} Ser phosphorylation site {S3199} coiled coil {3249-3282} glutamine-rich region {3261-4275} MOTIF: glutamine residue (SEVERAL) coiled coil {3562-3614} coiled coil {3714-3750} coiled coil {3897-3975} Ser phosphorylation site {S4215} LXXLL motif 3 {4222-4236} proline-rich region SITE: 4241-4360 MOTIF: proline residue (SEVERAL) LXXLL motif 4 {4253-4257} Ser phosphorylation site {S4359} LXXLL motif 5 {4463-4467} Ser phosphorylation site {S4738} Ser phosphorylation site {S4822} proline-rich region SITE: 4909-4977 MOTIF: proline residue (SEVERAL) LXXLL motif 6 {4990-4994} RING-finger {5092-5137} EFFECTOR-BOUND: Zn+2 FOR-BINDING-OF: DNA motif FYR N-terminal {5175-5235} FYR C-terminal {5236-5321} SET domain {5397-5513} MOTIF: binding site SITE: 5451-5451 FOR-BINDING-OF: S-adenosylmethionine S-adenosyl-L-methionine binding {5474-5475} Zn+2-binding site SITE: 5477-5477 post-SET domain {5521-5537} MOTIF: Zn+2-binding site SITE: 5525-5525 Zn+2-binding site SITE: 5527-5527 Zn+2-binding site SITE: 5532-5532

Database Correlations

OMIM 602113 UniProt O14686 PFAM correlations Entrez Gene 8085 Kegg hsa:8085 ENZYME 2.1.1.43