BioPAX pathway converted from "Core MLL complex, SMYD3, PRDM9 methylate dimethyl-lysine-5 of histone H3 (H3K4)" in the Reactome database.LEFT-TO-RIGHT2.1.1.43Core MLL complex, SMYD3, PRDM9 methylate Me2K5-histone H3Core MLL complex, SMYD3, PRDM9 methylate dimethyl-lysine-5 of histone H3 (H3K4)Trimethylation of lysine-5 of histone H3 (H3K4) has been linked to transcriptional activation in a variety of eukaryotic species (Ruthenberg et al. 2007). Several H3K4 methyltransferases have been identified in mammals, predominantly members of the Mixed Lineage Leukemia (MLL) protein family. Five of these, KMT2A (MML1), KMT2D (MLL2), KMT2C (MLL3), KMT2B (MLL4) and SETD1A (KMT2F) have been shown to display H3K4 mono-, di- and tri-methyltransferase activity (Milne et al. 2002, Hughes et al. 2004, Cho et al. 2007, Wysocka et al. 2003). KMT2G (SETD1B) is believed to have similar activity on the basis of sequence homology (Ruthenberg et al. 2007). MLLs are a component of large multiprotein complexes that also include WDR5, RBBP5, ASH2 and DPY30, assembled to form the core MLL complex (Nakamura et al. 2002, Hughes et al. 2004, Dou et al. 2006, Tremblay et al. 2014). The WD40 domain of WDR5 recognizes and binds the histone H3 N-terminus, presenting the lysine-4 side chain for methylation by one of the catalytically active MLL family (Couture et al. 2006, Ruthenburg et al. 2006). Histone H3 recognition by WDR5 is regulated by the methylation state of the adjacent arginine (H3R2) residue. H3R2 methylation abolishes WDR5 interaction with the H3 histone tail (Couture et al. 2006); H3K4 di-/trimethylation and H3R2 methylation have an inverse relationship (Guccione et al. 2006). <br><br>SMYD3 (KMT3E) and PRDM9 (KMT8B) are able to tri-methylate H3K4 (Hamamoto et al. 2004, Hayashi et al. 2005, Koh-Stenta et al. 2014).Authored: Jupe, S, 2013-03-12Reviewed: Motamedi, Mo, 2014-11-17Edited: Jupe, Steve, 2014-09-10SAMAdoMetS-adenosylmethionineS-adenosyl-L-methionineReactome DB_ID: 77087nucleoplasmGENE ONTOLOGYGO:0005654S-adenosyl-L-methionine [ChEBI:15414]S-adenosyl-L-methionineChEBICHEBI:15414Reactome Database ID Release 7577087Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=77087ReactomeR-ALL-770873Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-77087.3Reactomehttp://www.reactome.orgCOMPOUNDC00019additional informationMIMI:0361Converted from EntitySet in ReactomeMe2K5-histone H3Me2K5-replicative histone H3Me2K5-HIST1H3A,Me2K5-HIST2H3AMe2K5-replication-dependent histone H3Reactome DB_ID: 5244740HIST1H3AMe2K5-HIST1H3AHistone H3.1 with dimethylated lysine-4H31_HUMANReactome DB_ID: 1214170UniProt:P68431 H3C1H3C1H3FAHIST1H3AH3C2H3FLHIST1H3BH3C3H3FCHIST1H3CH3C4H3FBHIST1H3DH3C6H3FDHIST1H3EH3C7H3FIHIST1H3FH3C8H3FHHIST1H3GH3C10H3FKHIST1H3HH3C11H3FFHIST1H3IH3C12H3FJHIST1H3JFUNCTION Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.SUBUNIT The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.DEVELOPMENTAL STAGE Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.PTM Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.PTM Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.PTM Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.PTM Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.PTM Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Thr-12 (H3T11ph) by chromatin-associated CHEK1 regulates the transcription of cell cycle regulatory genes by modulating acetylation of Lys-10 (H3K9ac). Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.PTM Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination (By similarity). Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins.PTM Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression.PTM Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.PTM Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.PTM Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes (PubMed:29211711). It gives a specific tag for epigenetic transcription activation (PubMed:29211711). Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair (PubMed:27436229).PTM Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:30257210). Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac) (PubMed:30257210).DISEASE HIST1H3B or HIST1H3C mutations affecting residue Lys-37 of histone H3.1 are involved in the pathogenesis of pediatric undifferentiated soft tissue sarcomas. The mechanism through which mutations lead to tumorigenesis involves altered histones methylation with gain of global H3K27 methylation, altered Polycomb repressive complex 1 (PRC1) activity, aberrant epigenetic regulation of gene expression and impaired differentiation of mesenchimal progenitor cells.MISCELLANEOUS This histone is only present in mammals and is enriched in acetylation of Lys-15 and dimethylation of Lys-10 (H3K9me2).SIMILARITY Belongs to the histone H3 family.CAUTION The original paper reporting lysine deamination at Lys-5 by LOXL2 has been retracted due to inappropriate manipulation of figure data (PubMed:22483618, PubMed:27392148). However, this modification was confirmed in a subsequent publication (PubMed:27735137).Homo sapiensNCBI Taxonomy9606UniProtP684315EQUALN6,N6-dimethyl-L-lysineMODMOD:000842EQUAL136EQUALReactome Database ID Release 751214170Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1214170ReactomeR-HSA-12141701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1214170.1HIST2H3AMe2K5-HIST2H3AHistone H3.2 with dimethylated lysine-4H32_HUMANReactome DB_ID: 1214225UniProt:Q71DI3 H3C15H3C15HIST2H3AH3C14H3F2H3FMHIST2H3CH3C13HIST2H3DFUNCTION Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.SUBUNIT The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. During nucleosome assembly the chaperone ASF1A interacts with the histone H3-H4 heterodimer.DEVELOPMENTAL STAGE Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.PTM Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.PTM Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.PTM Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.PTM Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.PTM Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.PTM Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins.PTM Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression.PTM Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.PTM Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.PTM Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes (PubMed:29211711). It gives a specific tag for epigenetic transcription activation (PubMed:29211711). Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair (PubMed:27436229).PTM Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802). Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac) (PubMed:30257210).SIMILARITY Belongs to the histone H3 family.CAUTION The original paper reporting lysine deamination at Lys-5 by LOXL2 has been retracted due to inappropriate manipulation of figure data (PubMed:22483618, PubMed:27392148). However, this modification was confirmed in a subsequent publication (PubMed:27735137).UniProtQ71DI35EQUAL2EQUAL136EQUALReactome Database ID Release 751214225Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1214225ReactomeR-HSA-12142251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1214225.1Reactome Database ID Release 755244740Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244740ReactomeR-HSA-52447402Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244740.2SAHAdoHcyS-adenosylhomocysteineS-adenosyl-L-homocysteineReactome DB_ID: 77502S-adenosyl-L-homocysteine [ChEBI:16680]S-adenosyl-L-homocysteineChEBICHEBI:16680Reactome Database ID Release 7577502Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=77502ReactomeR-ALL-775023Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-77502.3COMPOUNDC00021Converted from EntitySet in ReactomeMe3K5-histone H3Me3K5-replicative histone H3Me3K5-replication-dependent histone H3Me3K5-HIST1H3A,Me3K5-HIST2H3AReactome DB_ID: 5244761HIST2H3AMe3K5-HIST2H3AHistone H3.2 with trimethylated lysine-4H32_HUMANReactome DB_ID: 12142235EQUALN6,N6,N6-trimethyl-L-lysineMODMOD:000832EQUAL136EQUALReactome Database ID Release 751214223Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1214223ReactomeR-HSA-12142231Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1214223.1HIST1H3AMe3K5-HIST1H3AHistone H3.1 with trimethylated lysine-4H31_HUMANReactome DB_ID: 12141865EQUAL2EQUAL136EQUALReactome Database ID Release 751214186Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1214186ReactomeR-HSA-12141861Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1214186.1Reactome Database ID Release 755244761Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244761ReactomeR-HSA-52447612Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244761.2ACTIVATIONConverted from EntitySet in ReactomeCore MLL complex, SMYD3, PRDM9Reactome DB_ID: 5637685Core MLL complexReactome DB_ID: 5244738WDR5WD repeat-containing protein 5BMP2-induced 3-kb gene proteinBIG3Reactome DB_ID: 1629838UniProt:P61964 WDR5WDR5BIG3FUNCTION Contributes to histone modification (PubMed:19131338, PubMed:19556245, PubMed:19103755, PubMed:20018852, PubMed:16600877, PubMed:16829960). May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4' (PubMed:16829960). As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3 (PubMed:19556245). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (PubMed:18840606). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:19103755, PubMed:20018852). May regulate osteoblasts differentiation (By similarity). In association with RBBP5 and ASH2L, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653).SUBUNIT Interacts with PAXBP1; the interaction is direct and links a WDR5-containing histone methyltransferase complex to PAX7 and PAX3 (By similarity). Interacts with HCFC1 (PubMed:12670868). Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (PubMed:19103755). Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 (PubMed:16253997, PubMed:17355966, PubMed:17998332, PubMed:18838538). Core component of several methyltransferase-containing complexes including MLL1/MLL, MLL2/3 (also named ASCOM complex) and MLL4/WBP7 (PubMed:15199122, PubMed:15960975, PubMed:17021013, PubMed:17500065). Each complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), and the facultative components PAGR1, BAP18, CHD8, E2F6, HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, MYST1/MOF, NCOA6, PAXIP1/PTIP, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9, TEX10 and alpha- and beta-tubulin (PubMed:14992727, PubMed:18378692). Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 (PubMed:20018852). Interacts with KMT2A/MLL1 (via WIN motif) and RBBP5; the interaction is direct (PubMed:19556245, PubMed:21220120, PubMed:22665483, PubMed:22266653, PubMed:18840606, PubMed:18829459). Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 (PubMed:19103755). In the complex, it probably interacts directly with KAT2A, MBIP and KAT14 (PubMed:19103755). Interacts with histone H3 (PubMed:16946699, PubMed:16600877, PubMed:16829960, PubMed:16829959). Interacts with SETD1A (via WIN motif) (PubMed:17998332, PubMed:22665483, PubMed:22266653). Component of a histone methylation complex composed of at least ZNF335, RBBP5, ASH2L and WDR5; the complex may have histone H3-specific methyltransferase activity, however does not have specificity for 'Lys-4' of histone H3 (PubMed:19131338). Interacts with ZNF335 (PubMed:19131338, PubMed:23178126). Components of this complex may associate with components of the ZNF335-CCAR2-EMSY nuclear receptor-mediated transcription complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5 (PubMed:19131338). Interacts with PER1 (By similarity). Interacts with KMT2B (via WIN motif), KMT2C (via WIN motif), KMT2D (via WIN motif) and SETD1B (via WIN motif) (PubMed:22665483, PubMed:22266653, PubMed:18840606).SIMILARITY Belongs to the WD repeat WDR5/wds family.UniProtP619642EQUAL334EQUALReactome Database ID Release 751629838Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1629838ReactomeR-HSA-16298382Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1629838.21ASH2LSet1/Ash2 histone methyltransferase complex subunit ASH2ASH2-like proteinASH2L1Reactome DB_ID: 1629834UniProt:Q9UBL3 ASH2LASH2LASH2L1FUNCTION Transcriptional regulator (PubMed:12670868). Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters (PubMed:19131338). Component of the Set1/Ash2 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is already methylated (PubMed:19556245). As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3 (PubMed:19556245). May play a role in hematopoiesis (PubMed:12670868). In association with RBBP5 and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653).SUBUNIT Interacts with HCFC1 (PubMed:12670868). Core component of several methyltransferase-containing complexes including MLL1/MLL, MLL2/3 (also named ASCOM complex) and MLL4/WBP7 (PubMed:15199122, PubMed:15960975, PubMed:17500065). Each complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), and the facultative components PAGR1, BAP18, CHD8, E2F6, HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, KAT8/MOF, NCOA6, PAXIP1/PTIP, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9, TEX10 and alpha- and beta-tubulin (PubMed:14992727, PubMed:15199122, PubMed:15960975, PubMed:17500065). Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 (PubMed:16253997, PubMed:17355966, PubMed:17998332, PubMed:18838538). Found in a complex with RBBP5, ASH2L, DPY30, KMT2A, KMT2D and WDR5 (By similarity). Component of a histone methylation complex composed of at least ZNF335, RBBP5, ASH2L and WDR5; the complex may have histone H3-specific methyltransferase activity, however does not have specificity for 'Lys-4' of histone H3 (PubMed:19131338). Within the complex, interacts with ZNF335 (PubMed:19131338). Interacts with RBBP5 (PubMed:19131338, PubMed:19556245, PubMed:21220120). Components of this complex may associate with components of a nuclear receptor-mediated transcription complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5 (PubMed:19131338). Within this complex also interacts with CCAR2 and EMSY (PubMed:19131338). Interacts with DPY30 (PubMed:19556245). Interacts with SETD1A and SETD1B (PubMed:17998332).TISSUE SPECIFICITY Ubiquitously expressed. Predominantly expressed in adult heart and testis and fetal lung and liver, with barely detectable expression in adult lung, liver, kidney, prostate, and peripheral leukocytes.PTM Both monomethylated and dimethylated on arginine residues in the C-terminus. Arg-296 is the major site. Methylation is not required for nuclear localization, nor for MLL complex integrity or maintenance of global histone H3K4me3 levels.UniProtQ9UBL31EQUAL628EQUALReactome Database ID Release 751629834Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1629834ReactomeR-HSA-16298341Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1629834.11Converted from EntitySet in ReactomeKMT2A-E, SETD1A,(SETD1B)Reactome DB_ID: 5244745KMT2FSETD1AHistone-lysine N-methyltransferase SETD1ASET1A_HUMANReactome DB_ID: 3239027UniProt:O15047 SETD1ASETD1AKIAA0339KMT2FSET1SET1AFUNCTION Histone methyltransferase that specifically methylates 'Lys-4' of histone H3, when part of the SET1 histone methyltransferase (HMT) complex, but not if the neighboring 'Lys-9' residue is already methylated. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. The non-overlapping localization with SETD1B suggests that SETD1A and SETD1B make non-redundant contributions to the epigenetic control of chromatin structure and gene expression.SUBUNIT Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30. Interacts with HCFC1. Interacts with ASH2/ASH2L, CXXC1/CFP1 and RBBP5. Interacts (via the RRM domain) with WDR82. Interacts (via the RRM domain) with hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A) only in the presence of WDR82. Binds specifically to CTD heptad repeats phosphorylated on 'Ser-5' of each heptad. Interacts with ZNF335. Interacts with SUPT6H. Interacts with NAP1L1 (By similarity). Interacts (via WIN motif) with WDR5 (PubMed:17998332, PubMed:22665483, PubMed:22266653).SIMILARITY Belongs to the class V-like SAM-binding methyltransferase superfamily.UniProtO150471EQUAL1707EQUALReactome Database ID Release 753239027Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3239027ReactomeR-HSA-32390271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3239027.1MLLKMT2AMLL1Histone-lysine N-methyltransferase MLLMLL1_HUMANReactome DB_ID: 1183223UniProt:Q03164 KMT2AKMT2AALL1CXXC7HRXHTRXMLLMLL1TRX1FUNCTION Histone methyltransferase that plays an essential role in early development and hematopoiesis. Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac). In the MLL1/MLL complex, it specifically mediates H3K4me, a specific tag for epigenetic transcriptional activation (PubMed:12453419, PubMed:20677832, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9'. Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20677832, PubMed:20010842). Promotes PPP1R15A-induced apoptosis. Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-ARNTL/BMAL1 heterodimer. Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-ARNTL/BMAL1 to chromatin (By similarity).SUBUNIT MLL cleavage product N320 heterodimerizes with MLL cleavage product C180 (via SET and FYRC domains). Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, HCFC2, WDR5, DPY30 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (PubMed:15199122, PubMed:15960975, PubMed:17500065, PubMed:19556245, PubMed:19187761, PubMed:26886794). Interacts (via WIN motif) with WDR5; the interaction is direct (PubMed:19556245, PubMed:18829459, PubMed:22665483, PubMed:18840606). Interaction with WDR5 is required for stable interaction with ASH2L and RBBP5, and thereby also for optimal histone methyltransferase activity (PubMed:26886794). Interacts with KAT8/MOF; the interaction is direct (PubMed:15960975). Interacts with SBF1 and PPP1R15A (PubMed:9537414, PubMed:10490642). Interacts with ZNF335 (PubMed:23178126). Interacts with CLOCK and ARNTL/BMAL1 in a circadian manner (By similarity). Interacts with PPIE; this results in decreased histone H3 methyltransferase activity (PubMed:20677832, PubMed:20541251). Interacts with CREBBP (PubMed:16253272). Interacts with the WRAD complex composed of WDR5, RBBP5, ASH2L and DPY30 (PubMed:22665483). Interacts (via MBM motif) with MEN1 (PubMed:22936661, PubMed:22327296, PubMed:25305204). Interacts (via IBM motifs) with PSIP1 (via IBD domain) with moderate affinity whereas the KMT2A-MEN1 complex interacts with a greater affinity; MEN1 enhances interaction of KMT2A with PSIP1 (PubMed:22327296, PubMed:25305204, PubMed:25082813, PubMed:29997176). Phosphorylation increases its affinity for PSIP1 (PubMed:29997176). Forms a complex with CREBBP and CREB1 (PubMed:23651431).TISSUE SPECIFICITY Heart, lung, brain and T- and B-lymphocytes.DOMAIN The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.DOMAIN The SET domain structure is atypical and is not in an optimal position to have methyltransferase activity. It requires other components of the MLL1/MLL complex, such as ASH2L or RBBP5, to order the active site and obtain optimal histone methyltransferase activity.DOMAIN The CXXC-type zinc finger binds to DNA sequence elements containing unnmethylated CpG dinucleotides.DOMAIN The third PHD-type zinc-finger binds both trimethylated histone H3K4me3 and PPIE; histone and PPIE bind to distinct surfaces (PubMed:20677832, PubMed:20541251). Nevertheless, PPIE binding and histone binding are mutually inhibitory (PubMed:20677832). Isomerization of a peptidylproline bond in the linker between the third PHD-type zinc-finger and the bromo domain disrupts the interaction between the bromo domain and the third PHD-type zinc-finger, and thereby facilitates interaction with PPIE (PubMed:20541251).PTM Proteolytic cleavage by TASP1 generates MLL cleavage product N320 and MLL cleavage product C180, which reassemble through a non-covalent association. 2 cleavage sites exist, cleavage site 1 (CS1) and cleavage site 2 (CS2), to generate MLL cleavage products N320 and C180. CS2 is the major site.PTM Phosphorylation increases its interaction with PSIP1.DISEASE Chromosomal aberrations involving KMT2A are a cause of acute leukemias. Translocation t(1;11)(q21;q23) with MLLT11/AF1Q; translocation t(3;11)(p21;q23) with NCKIPSD/AF3p21; translocation t(3,11)(q25,q23) with GMPS; translocation t(4;11)(q21;q23) with AFF1/MLLT2/AF4; insertion ins(5;11)(q31;q13q23) with AFF4/AF5Q31; translocation t(5;11)(q12;q23) with AF5-alpha/CENPK; translocation t(6;11)(q27;q23) with AFDN; translocation t(9;11)(p22;q23) with MLLT3/AF9; translocation t(10;11)(p11.2;q23) with ABI1; translocation t(10;11)(p12;q23) with MLLT10/AF10; t(11;15)(q23;q14) with KNL1 and ZFYVE19; translocation t(11;17)(q23;q21) with MLLT6/AF17; translocation t(11;19)(q23;p13.3) with ELL; translocation t(11;19)(q23;p13.3) with MLLT1/ENL; translocation t(11;19)(q23;p23) with GAS7; translocation t(X;11)(q13;q23) with FOXO4/AFX1. Translocation t(3;11)(q28;q23) with LPP. Translocation t(10;11)(q22;q23) with TET1. Translocation t(9;11)(q34;q23) with DAB2IP. Translocation t(4;11)(p12;q23) with FRYL. Fusion proteins KMT2A-MLLT1, KMT2A-MLLT3 and KMT2A-ELL interact with PPP1R15A and, on the contrary to unfused KMT2A, inhibit PPP1R15A-induced apoptosis. Fusion protein KMT2A-MLLT3 interacts with MEN1 and PSIP1 (PubMed:22936661, PubMed:25305204).DISEASE A chromosomal aberration involving KMT2A may be a cause of chronic neutrophilic leukemia. Translocation t(4;11)(q21;q23) with SEPT11.SIMILARITY Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily.UniProtQ031641EQUAL3969EQUALReactome Database ID Release 751183223Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1183223ReactomeR-HSA-11832231Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1183223.1WBP7KMT2BHistone-lysine N-methyltransferase MLL4WBP7MLL4_HUMANReactome DB_ID: 1183216UniProt:Q9UMN6 KMT2BKMT2BHRX2KIAA0304MLL2MLL4TRX2WBP7FUNCTION Histone methyltransferase that methylates 'Lys-4' of histone H3 (PubMed:17707229). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (PubMed:17707229). Plays a central role in beta-globin locus transcription regulation by being recruited by NFE2 (PubMed:17707229). Plays an important role in controlling bulk H3K4me during oocyte growth and preimplantation development (By similarity). Required during the transcriptionally active period of oocyte growth for the establishment and/or maintenance of bulk H3K4 trimethylation (H3K4me3), global transcriptional silencing that preceeds resumption of meiosis, oocyte survival and normal zygotic genome activation (By similarity).SUBUNIT Component of the menin-associated histone methyltransferase complex, at least composed of KMT2B/MLL4, ASH2L, RBBP5, WDR5, DPY30, MEN1; the complex interacts with POLR2A and POLR2B via MEN1. Interacts with NFE2. Interacts with KDM6B. Interacts (via WIN motif) with WDR5 (PubMed:22665483, PubMed:22266653, PubMed:18840606). Interacts (via MBM motif) with MEN1 (PubMed:22327296).TISSUE SPECIFICITY Widely expressed. Highest levels in testis. Also found in brain with higher expression in the cerebellum than in any other region, bone marrow, heart, muscle, kidney, placenta, spleen, thymus, prostate, ovary, intestine, colon, peripheral blood lymphocytes and pancreas. Often amplified in pancreatic carcinomas.DOMAIN The CXXC zinc finger mediates binding to DNA containing unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides.SIMILARITY Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily.CAUTION This protein was first named MLL2 by PubMed:10637508 and PubMed:10409430. MLL2 corresponds to another protein located on chromosome 12 (see AC O14686). Thus, KMT2B/MLL4 is often referred to as MLL2 and vice versa in the literature.UniProtQ9UMN62EQUAL2715EQUALReactome Database ID Release 751183216Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1183216ReactomeR-HSA-11832161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1183216.1MLL3KMT2CHistone-lysine N-methyltransferase MLL3MLL3_HUMANReactome DB_ID: 1183224UniProt:Q8NEZ4 KMT2CKMT2CHALRKIAA1506MLL3FUNCTION Histone methyltransferase that methylates 'Lys-4' of histone H3 (PubMed:22266653). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Central component of the MLL2/3 complex, a coactivator complex of nuclear receptors, involved in transcriptional coactivation. KMT2C/MLL3 may be a catalytic subunit of this complex. May be involved in leukemogenesis and developmental disorder.SUBUNIT Component of the MLL2/3 complex (also named ASCOM complex), at least composed of KMT2D/MLL2 or KMT2C/MLL3, ASH2L, RBBP5, WDR5, NCOA6, DPY30, KDM6A, PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin. Interacts with histone H3. Interacts (via WIN motif) with WDR5 (PubMed:22665483, PubMed:22266653).TISSUE SPECIFICITY Highly expressed in testis and ovary, followed by brain and liver. Also expressed in placenta, peripherical blood, fetal thymus, heart, lung and kidney. Within brain, expression was highest in hippocampus, caudate nucleus, and substantia nigra. Not detected in skeletal muscle and fetal liver.DOMAIN The SET domain interacts with histone H3 but not H2A, H2B and H4, and may have a H3 lysine specific methylation activity.MISCELLANEOUS Found in a critical region of chromosome 7, which is commonly deleted in malignant myeloid disorders. Partial duplication of the KMT2C gene are found in the juxtacentromeric region of chromosomes 1, 2, 13 and 21. Juxtacentromeric reshuffling of the KMT2C gene has generated the BAGE genes.SIMILARITY Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily.UniProtQ8NEZ41EQUAL4911EQUALReactome Database ID Release 751183224Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1183224ReactomeR-HSA-11832241Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1183224.1MLL2KMT2DHistone-lysine N-methyltransferase MLL2MLL2_HUMANReactome DB_ID: 1183219UniProt:O14686 KMT2DKMT2DALRMLL2MLL4FUNCTION 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.SUBUNIT Component of the MLL2/3 complex (also named ASCOM complex), at least composed of KMT2D/MLL2 or KMT2C/MLL3, ASH2L, RBBP5, WDR5, NCOA6, DPY30, KDM6A, PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin. Interacts with ESR1; interaction is direct. Interacts (via WIN motif) with WDR5 (PubMed:22665483, PubMed:22266653).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.MISCELLANEOUS This gene mapped to a chromosomal region involved in duplications and translocations associated with cancer.SIMILARITY Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily.CAUTION Another protein KMT2B/MLL4, located on chromosome 19, was first named MLL2 (see AC Q9UMN6). Thus, KMT2B/MLL4 is often referred to as MLL2 and vice versa in the literature.UniProtO146861EQUAL5537EQUALReactome Database ID Release 751183219Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1183219ReactomeR-HSA-11832191Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1183219.1MLL5KMT2EHistone-lysine N-methyltransferase MLL5MLL5_HUMANReactome DB_ID: 1183225UniProt:Q8IZD2 KMT2EKMT2EMLL5FUNCTION 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).SUBUNIT 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).TISSUE SPECIFICITY 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).DOMAIN The PHD-type domain binds specifically histone H3 tri-methylated at 'Lys-4' (H3K4me3), thus promoting binding to chromatin.DOMAIN 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.DOMAIN The C-terminus domain is responsible for the localization to the centrosome during mitosis.PTM Ubiquitinated. Deubiquitinated by USP7.PTM O-glycosylated at Ser-435 and Thr-440 in the SET domain by OGT which probably prevents KMT2E proteasomal-mediated degradation.SIMILARITY Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily.CAUTION 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).UniProtQ8IZD21EQUAL1858EQUALReactome Database ID Release 751183225Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1183225ReactomeR-HSA-11832251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1183225.1KMT2GSETD1BHistone-lysine N-methyltransferase SETD1B ecNumber2.1.1.43/ecNumberSET1B_HUMANReactome DB_ID: 5244714UniProt:Q9UPS6 SETD1BSETD1BKIAA1076KMT2GSET1BFUNCTION Histone methyltransferase that specifically methylates 'Lys-4' of histone H3, when part of the SET1 histone methyltransferase (HMT) complex, but not if the neighboring 'Lys-9' residue is already methylated. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. The non-overlapping localization with SETD1A suggests that SETD1A and SETD1B make non-redundant contributions to the epigenetic control of chromatin structure and gene expression. Specifically tri-methylates 'Lys-4' of histone H3 in vitro.SUBUNIT Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30. Interacts with HCFC1 and ASH2L/ASH2. Interacts (via the RRM domain) with WDR82. Interacts (via the RRM domain) with hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A) only in the presence of WDR82. Binds specifically to CTD heptad repeats phosphorylated on 'Ser-5' of each heptad. Interacts with RBM15. Interacts (via WIN motif) with WDR5 (PubMed:22665483, PubMed:22266653).SIMILARITY Belongs to the class V-like SAM-binding methyltransferase superfamily.UniProtQ9UPS61EQUAL1923EQUALReactome Database ID Release 755244714Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244714ReactomeR-HSA-52447141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244714.1Reactome Database ID Release 755244745Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244745ReactomeR-HSA-52447451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244745.11RBQ3RBBP5Retinoblastoma-binding protein 5RBBP-5Retinoblastoma-binding protein RBQ-3Reactome DB_ID: 1629836UniProt:Q15291 RBBP5RBBP5RBQ3FUNCTION In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci, including that mediated by retinoic acid (By similarity). Does not affect ES cell self-renewal (By similarity). Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters (PubMed:19131338). As part of the MLL1/MLL complex, involved in mono-, di- and trimethylation at 'Lys-4' of histone H3 (PubMed:19556245). Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (PubMed:19556245). In association with ASH2L and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:22266653, PubMed:21220120).SUBUNIT Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 (PubMed:16253997, PubMed:17355966, PubMed:17998332, PubMed:18838538). Core component of several methyltransferase-containing complexes including MLL1/MLL, MLL2/3 (also named ASCOM complex) and MLL4/WBP7 (PubMed:15199122, PubMed:15960975, PubMed:17500065). Each complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), and the facultative components PAGR1, BAP18, CHD8, E2F6, HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, MYST1/MOF, NCOA6, PAXIP1/PTIP, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9, TEX10 and alpha- and beta-tubulin (PubMed:14992727, PubMed:15199122, PubMed:15960975, PubMed:17500065). Component of a histone methylation complex composed of at least ZNF335, RBBP5, ASH2L and WDR5; the complex may have histone H3-specific methyltransferase activity, however does not have specificity for 'Lys-4' of histone H3 (PubMed:19131338). Interacts with ZNF335 (PubMed:19131338, PubMed:23178126). Interacts with ASH2L; the interaction is direct (PubMed:19131338, PubMed:19556245, PubMed:21220120). Interacts with WDR5; the interaction is direct (PubMed:19556245, PubMed:21220120). Components of the ZNF335-RBBP5-ASH2L-WDR5 histone methylation complex may associate with components of a nuclear receptor-mediated transcription complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5 (PubMed:19131338). Within this complex interacts with EMSY (PubMed:19131338). Found in a complex with RBBP5, ASH2L, DPY30, KMT2A, KMT2D and WDR5 (By similarity). Interacts with SETD1A (PubMed:17998332). Interacts with WDR82 (PubMed:18838538).TISSUE SPECIFICITY Ubiquitously expressed.UniProtQ152911EQUAL538EQUALReactome Database ID Release 751629836Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1629836ReactomeR-HSA-16298361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1629836.11DPY30Protein dpy-30 homologDPY30_HUMANReactome DB_ID: 5669104UniProt:Q9C005 DPY30DPY30FUNCTION As part of the MLL1/MLL complex, involved in the methylation of histone H3 at 'Lys-4', particularly trimethylation. Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. May play some role in histone H3 acetylation. In a teratocarcinoma cell, plays a crucial role in retinoic acid-induced differentiation along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci. May also play an indirect or direct role in endosomal transport.SUBUNIT Homodimer. Core component of several methyltransferase-containing complexes including MLL1/MLL, MLL2/3 (also named ASCOM complex) and MLL4/WBP7. Each complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), and the facultative components MEN1, HCFC1, HCFC2, NCOA6, KDM6A, PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin (By similarity). Interacts with ASH2L; the interaction is direct. Interacts with ARFGEF1. Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30.SIMILARITY Belongs to the dpy-30 family.UniProtQ9C0051EQUAL99EQUALReactome Database ID Release 755669104Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5669104ReactomeR-HSA-56691041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5669104.11Reactome Database ID Release 755244738Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244738ReactomeR-HSA-52447381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244738.1SMYD3Histone-lysine N-methyltransferase SMYD3SMYD3_HUMANKMT3EReactome DB_ID: 5637688UniProt:Q9H7B4 SMYD3SMYD3ZMYND1ZNFN3A1FUNCTION Histone methyltransferase. Specifically methylates 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation (PubMed:15235609, PubMed:22419068). Also methylates 'Lys-5' of histone H4 (PubMed:22419068). Plays an important role in transcriptional activation as a member of an RNA polymerase complex (PubMed:15235609). Binds DNA containing 5'-CCCTCC-3' or 5'-GAGGGG-3' sequences (PubMed:15235609).ACTIVITY REGULATION Histone methyltransferase activity strongly stimulated by HSPCA.SUBUNIT Interacts with HSPCA (PubMed:15235609). Interacts with HELZ (PubMed:15235609). Interacts with POLR2A; the interaction may be indirect and may be mediated by HELZ (PubMed:15235609). Interacts with HSP90AA1; this interaction enhances SMYD3 histone-lysine N-methyltransferase (PubMed:25738358).TISSUE SPECIFICITY Expressed in skeletal muscles and testis. Overexpressed in a majority of colorectal and hepatocellular carcinomas.SIMILARITY Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family.UniProtQ9H7B41EQUAL428EQUALReactome Database ID Release 755637688Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5637688ReactomeR-HSA-56376881Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5637688.1PRDM9Histone-lysine N-methyltransferase PRDM9PRDM9_HUMANKMT8BReactome DB_ID: 912345UniProt:Q9NQV7 PRDM9PRDM9PFM6FUNCTION Histone methyltransferase that sequentially mono-, di-, and tri-methylates both 'Lys-4' (H3K4) and 'Lys-36' (H3K36) of histone H3 to produce respectively trimethylated 'Lys-4' (H3K4me3) and trimethylated 'Lys-36' (H3K36me3) histone H3 and plays a key role in meiotic prophase by determining hotspot localization thereby promoting meiotic recombination (PubMed:24634223, PubMed:24095733, PubMed:26833727). Also can methylate all four core histones with H3 being the best substrate and the most highly modified (PubMed:24095733, PubMed:24634223, PubMed:26833727). Is also able, on one hand, to mono and di-methylate H4K20 and on other hand to trimethylate H3K9 with the di-methylated H3K9 as the best substrate (By similarity). During meiotic prophase, binds specific DNA sequences through its zinc finger domains thereby determining hotspot localization where it promotes local H3K4me3 and H3K36me3 enrichment on the same nucleosomes through its histone methyltransferase activity (PubMed:26833727). Thereby promotes double-stranded breaks (DSB) formation, at this subset of PRDM9-binding sites, that initiates meiotic recombination for the proper meiotic progression (By similarity). During meiotic progression hotspot-bound PRDM9 interacts with several complexes; in early leptonema binds CDYL and EHMT2 followed by EWSR1 and CXXC1 by the end of leptonema. EWSR1 joins PRDM9 with the chromosomal axis through REC8 (By similarity). In this way, controls the DSB repair pathway, pairing of homologous chromosomes and sex body formation (By similarity). Moreover plays a central role in the transcriptional activation of genes during early meiotic prophase thanks to H3K4me3 and H3K36me3 enrichment that represents a specific tag for epigenetic transcriptional activation (By similarity). In addition performs automethylation (By similarity). Acetylation and phosphorylation of histone H3 attenuate or prevent histone H3 methylation (By similarity).ACTIVITY REGULATION Inhibited by suramin with an IC(50) of 4.1 uM.SUBUNIT Homodimer (PubMed:26833727, PubMed:24095733, Ref.9). Interacts with EHMT2 and CDYL; interaction only takes place when PRDM9 is bound to hotspot DNA. Interacts with CXXC1; this interaction does not link PRDM9-activated recombination hotspot sites with DSB machinery and is not required for the hotspot recognition pathway. Forms a complex with EWSR1, REC8, SYCP3 and SYCP1; complex formation is dependent of phosphorylated form of REC8 and requires PRDM9 bound to hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8 (By similarity).DOMAIN The C2H2-type zinc fingers determine the hotspot localization through its binding to specific DNA sequences. Variations in their sequence affect affinity towards DNA-binding motif.PTM Mono-methylated; automethylated. Tri-methylated; automethylated. Mono-methylation is predominant; automethylation is lower and slower than H3 peptide methylation and is in a highest S-adenosyl-L-methionine concentration-dependent. There are two major sites for automethylation at Lys-368 and Lys-374. Lysines can be simultaneously methylated, such as Lys-368(me3)/Lys-372(me1), Lys-368(me1)/Lys-374(me1) and Lys-368(me1)/Lys-372(me1)/Lys-374(me1). Automethylation is an intramolecular (cis) process.POLYMORPHISM Several alleles exist depending on both the number of zinc finger C2H2 type domains and their identity (PubMed:26833727). Each allele binds to a specific hotspot set (PubMed:26833727). Variations in the zinc finger C2H2 type domains are associated with significant differences in affinity towards DNA-binding motif (PubMed:26833727). The sequence shown is that of allele B.SIMILARITY Belongs to the class V-like SAM-binding methyltransferase superfamily.UniProtQ9NQV71EQUAL894EQUALReactome Database ID Release 75912345Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=912345ReactomeR-HSA-9123451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-912345.1Reactome Database ID Release 755637685Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5637685ReactomeR-HSA-56376851Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5637685.1GENE ONTOLOGYGO:0018024gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 755244706Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244706Reactome Database ID Release 755244692Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244692ReactomeR-HSA-52446923Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244692.316767079Pubmed2006Myc-binding-site recognition in the human genome is determined by chromatin contextGuccione, ErnestoMartinato, FrancescaFinocchiaro, GiacomoLuzi, LucillaTizzoni, LauraDall' Olio, ValentinaZardo, GiuseppeNervi, ClaraBernard, LorisAmati, BrunoNat. Cell Biol. 8:764-7014992727Pubmed2004Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locusHughes, Christina MRozenblatt-Rosen, OMilne, Thomas ACopeland, Terry DLevine, Stuart SLee, Jeffrey CHayes, D NeilShanmugam, Kalai SelviBhattacharjee, ArindamBiondi, Christine AKay, Graham FHayward, Nicholas KHess, Jay LMeyerson, MMol. Cell 13:587-9716292313Pubmed2005A histone H3 methyltransferase controls epigenetic events required for meiotic prophaseHayashi, KYoshida, KMatsui, YNature 438:374-817500065Pubmed2007PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complexCho, Young-WookHong, TeresaHong, SunhwaGuo, HongYu, HongKim, DoyeobGuszczynski, TadDressler, Gregory RCopeland, Terry DKalkum, MarkusGe, KaiJ. Biol. Chem. 282:20395-40624785241Pubmed2014Characterization of the histone methyltransferase PRDM9 using biochemical, biophysical and chemical biology techniquesKoh-Stenta, XiaoyingJoy, JomaPoulsen, AndersLi, RongTan, YvonneShim, YoonjungMin, Jung-HyunWu, LilingNgo, AnnaPeng, JianheSeetoh, Wei GuangCao, JingWee, John Liang KuanKwek, Perlyn ZekuiHung, AlvinLakshmanan, UmayalFlotow, HorstGuccione, ErnestoHill, JeffreyBiochem. J. 461:323-3416878130Pubmed2006Regulation of MLL1 H3K4 methyltransferase activity by its core componentsDou, YaliMilne, Thomas ARuthenburg, Alexander JLee, SeungheeLee, Jae WoonVerdine, GLAllis, C DavidRoeder, Robert GNat. Struct. Mol. Biol. 13:713-917021013Pubmed2006Coactivator as a target gene specificity determinant for histone H3 lysine 4 methyltransferasesLee, SeungheeLee, Dong-KeeDou, YaliLee, JeongkyungLee, BoraKwak, EunyeeKong, YYLee, Soo-KyungRoeder, Robert GLee, Jae WProc. Natl. Acad. Sci. U.S.A. 103:15392-717707229Pubmed2007Activator-mediated recruitment of the MLL2 methyltransferase complex to the beta-globin locusDemers, CelinaChaturvedi, Chandra-PrakashRanish, Jeffrey AJuban, GaetanLai, PatrickMorle, FrancoisAebersold, RuediDilworth, F JeffreyGroudine, MarkBrand, MarjorieMol. Cell 27:573-8417218268Pubmed2007Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic markRuthenburg, Alexander JAllis, C DavidWysocka, JoannaMol. Cell 25:15-3016829960Pubmed2006Molecular recognition of histone H3 by the WD40 protein WDR5Couture, Jean-FrançoisCollazo, EvysTrievel, Raymond CNat. Struct. Mol. Biol. 13:698-70312453419Pubmed2002ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulationNakamura, TatsuyaMori, ToshikiTada, ShinichiroKrajewski, WladyslawRozovskaia, TanyaWassell, RichardDubois, GarrettMazo, AlexanderCroce, CMCanaani, EliMol. Cell 10:1119-2816199523Pubmed2005MLL associates specifically with a subset of transcriptionally active target genesMilne, Thomas ADou, YaliMartin, Mary EllenBrock, Hugh WRoeder, Robert GHess, Jay LProc. Natl. Acad. Sci. U.S.A. 102:14765-7015235609Pubmed2004SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cellsHamamoto, RyujiFurukawa, YoichiMorita, MIimura, YukoSilva, Fabio PittellaLi, MeihuaYagyu, RyuichiroNakamura, YusukeNat. Cell Biol. 6:731-4016829959Pubmed2006Histone H3 recognition and presentation by the WDR5 module of the MLL1 complexRuthenburg, Alexander JWang, WooikoonGraybosch, Daina MLi, HaitaoAllis, C DavidPatel, Dinshaw JVerdine, GLNat. Struct. Mol. Biol. 13:704-1212670868Pubmed2003Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1Wysocka, JoannaMyers, Michael PLaherty, Carol DEisenman, Robert NHerr, WinshipGenes Dev. 17:896-91112453418Pubmed2002MLL targets SET domain methyltransferase activity to Hox gene promotersMilne, Thomas ABriggs, Scott DBrock, Hugh WMartin, Mary EllenGibbs, DeniseAllis, C DavidHess, Jay LMol. Cell 10:1107-17INHIBITIONReactome Database ID Release 755244782Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244782ReactomeR-HSA-52447821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244782.1Converted from EntitySet in ReactomeMe2aR3-histone H3, MeR3-histone H3Me2aR3-replicative histone H3, MeR3-replicative histone H3Me2aR3-replication-dependent histone H3, MeR3-replication-dependent histone H3Me3R-HIST1H3A,Me3R-HIST2H3A,Me2aR3-HIST1H3A,Me2aR3-HIST2H3AReactome DB_ID: 5244525Converted from EntitySet in ReactomeMeR3-histone H3MeR3-replicative histone H3Me3R-replication-dependent histone H3Me3R-HIST1H3A,Me3R-HIST2H3AReactome DB_ID: 5244521Histone H3aMeR3-HIST1H3AHistone H3.1Histone H3bHistone H3cHistone H3dHistone H3fHistone H3hHistone H3iHistone H3jHistone H3kHistone H3lReactome DB_ID: 52445293EQUALomega-N-methyl-L-arginineMODMOD:000782EQUAL136EQUALReactome Database ID Release 755244529Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244529ReactomeR-HSA-52445291Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244529.1HIST2H3CMeR3-HIST2H3AHistone H3.2HIST2H3DReactome DB_ID: 52445203EQUAL2EQUAL136EQUALReactome Database ID Release 755244520Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244520ReactomeR-HSA-52445201Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244520.1Reactome Database ID Release 755244521Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244521ReactomeR-HSA-52445212Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244521.2Converted from EntitySet in ReactomeMe2aR3-histone H3Me2aR3-replicative histone H3Me2aR3-HIST1H3A,Me2aR3-HIST2H3AMe2aR3-replication-dependent histone H3Reactome DB_ID: 5244522Histone H3aMe2aR3-HIST1H3AHistone H3.1Histone H3bHistone H3cHistone H3dHistone H3fHistone H3hHistone H3iHistone H3jHistone H3kHistone H3lReactome DB_ID: 52445263EQUALasymmetric dimethyl-L-arginineMODMOD:000772EQUAL136EQUALReactome Database ID Release 755244526Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244526ReactomeR-HSA-52445261Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244526.1Histone H3.2Me2aR3-HIST2H3AReactome DB_ID: 52445183EQUAL2EQUAL136EQUALReactome Database ID Release 755244518Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244518ReactomeR-HSA-52445181Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244518.1Reactome Database ID Release 755244522Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244522ReactomeR-HSA-52445221Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244522.1Reactome Database ID Release 755244525Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5244525ReactomeR-HSA-52445251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5244525.1