Human Gene KMT2D (ENST00000301067.12) from GENCODE V44
Description: Homo sapiens lysine methyltransferase 2D (KMT2D), mRNA. (from RefSeq NM_003482) RefSeq Summary (NM_003482): The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]. CCDS Note: The full-length exon combination of this CCDS representation is inferred. It is mostly supported by the mRNA AF010403.1, but with correction of a gap in exon 10-11, supported by the mRNA AF010404.1, and by EST, RNA-Seq and orthologous transcript alignments. ##RefSeq-Attributes-START## RefSeq Select criteria :: based on manual assertion, conservation ##RefSeq-Attributes-END## Gencode Transcript: ENST00000301067.12 Gencode Gene: ENSG00000167548.18 Transcript (Including UTRs) Position: hg38 chr12:49,018,978-49,060,794 Size: 41,817 Total Exon Count: 55 Strand: - Coding Region Position: hg38 chr12:49,021,780-49,055,324 Size: 33,545 Coding Exon Count: 54
ID:MLL2_HUMAN DESCRIPTION: RecName: Full=Histone-lysine N-methyltransferase MLL2; EC=2.1.1.43; AltName: Full=ALL1-related protein; AltName: Full=Lysine N-methyltransferase 2D; Short=KMT2D; AltName: Full=Myeloid/lymphoid or mixed-lineage leukemia protein 2; FUNCTION: Histone methyltransferase. Methylates 'Lys-4' of histone H3 (H3K4me). H3K4me represents a specific tag for epigenetic transcriptional activation. Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription. CATALYTIC ACTIVITY: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. SUBUNIT: Component of the MLL2/3 complex (also named ASCOM complex), at least composed of MLL2/ALR or MLL3, ASH2L, RBBP5, WDR5, NCOA6, DPY30, KDM6A, PAXIP1/PTIP, PAGR1 and alpha- and beta- tubulin. Interacts with ESR1; interaction is direct. INTERACTION: P03372:ESR1; NbExp=3; IntAct=EBI-996065, EBI-78473; Q14686:NCOA6; NbExp=6; IntAct=EBI-996065, EBI-78670; SUBCELLULAR LOCATION: Nucleus (Probable). TISSUE SPECIFICITY: Expressed in most adult tissues, including a variety of hematoipoietic cells, with the exception of the liver. DOMAIN: LXXLL motifs 5 and 6 are essential for the association with ESR1 nuclear receptor. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. DISEASE: Defects in MLL2 are the cause of Kabuki syndrome type 1 (KABUK1) [MIM:147920]. A congenital mental retardation syndrome with 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. MISCELLANEOUS: This gene mapped to a chromosomal region involved in duplications and translocations associated with cancer. SIMILARITY: Belongs to the histone-lysine methyltransferase family. TRX/MLL subfamily. SIMILARITY: Contains 1 FYR C-terminal domain. SIMILARITY: Contains 1 FYR N-terminal domain. SIMILARITY: Contains 5 PHD-type zinc fingers. SIMILARITY: Contains 1 post-SET domain. SIMILARITY: Contains 4 RING-type zinc fingers. SIMILARITY: Contains 1 SET domain. CAUTION: Another protein MLL4/WBP7, located on chromosome 19, was first named MLL2 (see AC Q9UMN6). Thus, MLL4 is often referred to as MLL2 and vice versa in the literature.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O14686
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Protein O14686 (Reactome details) participates in the following event(s):
R-HSA-3364014 Recruitment of SET1 methyltransferase complex R-HSA-3364026 SET1 complex trimethylates H3K4 at the MYC gene R-HSA-8935740 RUNX1 and GATA1 bind the promoter of the ITGA2B gene R-HSA-8936616 RUNX1 and GATA1 bind the promoter of the GP1BA gene R-HSA-8936979 RUNX1 and GATA1 bind the promoter of the THBS1 gene R-HSA-8937037 RUNX1 and GATA1 bind the promoter of the MIR27A gene R-HSA-8936481 Core MLL complex methylates H3K4Me2-Nucleosome at the ITGA2B gene promoter R-HSA-8936621 Core MLL complex methylates H3K4Me2-Nucleosome at the GP1BA gene promoter R-HSA-8937016 Core MLL complex methylates H3K4Me2-Nucleosome at the THBS1 gene promoter R-HSA-8937050 Core MLL complex methylates H3K4Me2-Nucleosome at the MIR27A gene promoter R-HSA-5159245 SETD3, SETD7 (KMT7), WHSC1L1 (KMT3F), Core MLL complex methylate lysine-5 of histone H3 (H3K4) R-HSA-5244692 Core MLL complex, SMYD3, PRDM9 methylate dimethyl-lysine-5 of histone H3 (H3K4) R-HSA-5637686 WHSC1L1 (KMT3F), Core MLL complex, SMYD3 (KMT3E) methylate methyl-lysine-5 of histone H3 (H3K4) R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex R-HSA-3769402 Deactivation of the beta-catenin transactivating complex R-HSA-201681 TCF dependent signaling in response to WNT R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis R-HSA-195721 Signaling by WNT R-HSA-8878171 Transcriptional regulation by RUNX1 R-HSA-5619507 Activation of HOX genes during differentiation R-HSA-162582 Signal Transduction R-HSA-3214841 PKMTs methylate histone lysines R-HSA-212436 Generic Transcription Pathway R-HSA-1266738 Developmental Biology R-HSA-3247509 Chromatin modifying enzymes R-HSA-73857 RNA Polymerase II Transcription R-HSA-4839726 Chromatin organization R-HSA-74160 Gene expression (Transcription)
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