ID KMT2A_HUMAN Reviewed; 3969 AA. AC Q03164; E9PQG7; Q13743; Q13744; Q14845; Q16364; Q59FF2; Q6UBD1; Q9HBJ3; AC Q9UD94; Q9UMA3; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2007, sequence version 5. DT 02-SEP-2026, entry version 269. DE RecName: Full=Histone-lysine N-methyltransferase 2A; DE Short=Lysine N-methyltransferase 2A; DE EC=2.1.1.364 {ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:25561738, ECO:0000269|PubMed:26886794}; DE AltName: Full=ALL-1 {ECO:0000303|PubMed:12453419}; DE AltName: Full=CXXC-type zinc finger protein 7; DE AltName: Full=Cysteine methyltransferase KMT2A {ECO:0000305}; DE EC=2.1.1.- {ECO:0000269|PubMed:24235145}; DE AltName: Full=Myeloid/lymphoid or mixed-lineage leukemia; DE AltName: Full=Myeloid/lymphoid or mixed-lineage leukemia protein 1; DE AltName: Full=Trithorax-like protein; DE AltName: Full=Zinc finger protein HRX; DE Contains: DE RecName: Full=MLL cleavage product N320; DE AltName: Full=N-terminal cleavage product of 320 kDa; DE Short=p320; DE Contains: DE RecName: Full=MLL cleavage product C180; DE AltName: Full=C-terminal cleavage product of 180 kDa; DE Short=p180; GN Name=KMT2A; Synonyms=ALL1, CXXC7, HRX, HTRX, MLL, MLL1, TRX1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1423624; DOI=10.1016/0092-8674(92)90602-9; RA Tkachuk D.C., Kohler S., Cleary M.L.; RT "Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal RT translocations in acute leukemias."; RL Cell 71:691-700(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3), AND VARIANT GLY-30. RX PubMed=8703835; DOI=10.1046/j.1365-2141.1996.d01-1748.x; RA Nilson I., Loechner K., Siegler G., Greil J., Beck J.D., Fey G.H., RA Marschalek R.; RT "Exon/intron structure of the human ALL-1 (MLL) gene involved in RT translocations to chromosomal region 11q23 and acute leukaemias."; RL Br. J. Haematol. 93:966-972(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-53; LYS-502; THR-2319; RP ARG-2354; ARG-2387; ILE-3714 AND ALA-3773. RG NIEHS SNPs program; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1909. RX PubMed=8378076; RA Yamamoto K., Seto M., Komatsu H., Iida S., Akao Y., Kojima S., Kodera Y., RA Nakazawa S., Ariyoshi Y., Takahashi T., Ueda R.; RT "Two distinct portions of LTG19/ENL at 19p13 are involved in t(11;19) RT leukemia."; RL Oncogene 8:2617-2625(1993). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 63-3969 (ISOFORM 3), AND CHROMOSOMAL RP TRANSLOCATION WITH AFF1/MLLT2. RX PubMed=1423625; DOI=10.1016/0092-8674(92)90603-a; RA Gu Y., Nakamura T., Alder H., Prasad R., Canaani O., Cimino G., Croce C.M., RA Canaani E.; RT "The t(4;11) chromosome translocation of human acute leukemias fuses the RT ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene."; RL Cell 71:701-708(1992). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 812-3969. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1112-1140 AND 1552-162, AND NUCLEOTIDE RP SEQUENCE [MRNA] OF 1317-2328. RC TISSUE=Brain; RX PubMed=1303259; DOI=10.1038/ng1092-113; RA Djabali M., Selleri L., Parry P., Bower M., Young B.D., Evans G.A.; RT "A trithorax-like gene is interrupted by chromosome 11q23 translocations in RT acute leukaemias."; RL Nat. Genet. 2:113-118(1992). RN [9] RP ERRATUM OF PUBMED:1303259. RX PubMed=8401594; DOI=10.1038/ng0893-431; RA Djabali M., Selleri L., Parry P., Bower M., Young B., Evans G.A.; RL Nat. Genet. 4:431-431(1993). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1212-1603 (ISOFORM 3). RX PubMed=7794749; DOI=10.1111/j.1365-2141.1995.tb05151.x; RA Marschalek R., Greil J., Lochner K., Nilson I., Siegler G., RA Zweckbronner I., Beck J.D., Fey G.H.; RT "Molecular analysis of the chromosomal breakpoint and fusion transcripts in RT the acute lymphoblastic SEM cell line with chromosomal translocation RT t(4;11)."; RL Br. J. Haematol. 90:308-320(1995). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1251-1654 (ISOFORM 2). RX PubMed=7598802; DOI=10.1089/dna.1995.14.475; RA Mbangkollo D., Burnett R., McCabe N., Thirman M., Gill H., Yu H., RA Rowley J.D., Diaz M.O.; RT "The human MLL gene: nucleotide sequence, homology to the Drosophila trx RT zinc-finger domain, and alternative splicing."; RL DNA Cell Biol. 14:475-483(1995). RN [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1251-1538. RX PubMed=8162575; RA Gu Y., Alder H., Nakamura T., Schichman S.A., Prasad R., Canaani O., RA Saito H., Croce C.M., Canaani E.; RT "Sequence analysis of the breakpoint cluster region in the ALL-1 gene RT involved in acute leukemia."; RL Cancer Res. 54:2327-2330(1994). RN [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1311-1687 (ISOFORM 3), AND CHROMOSOMAL RP TRANSLOCATION WITH GAS7. RX PubMed=10706619; DOI=10.1073/pnas.050397097; RA Megonigal M.D., Cheung N.-K.V., Rappaport E.F., Nowell P.C., Wilson R.B., RA Jones D.H., Addya K., Leonard D.G.B., Kushner B.H., Williams T.M., RA Lange B.J., Felix C.A.; RT "Detection of leukemia-associated MLL-GAS7 translocation early during RT chemotherapy with DNA topoisomerase II inhibitors."; RL Proc. Natl. Acad. Sci. U.S.A. 97:2814-2819(2000). RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1421-1540. RX PubMed=8414518; RA Forster A., Rabbitts T.H.; RT "A method for identifying genes within yeast artificial chromosomes: RT application to isolation of MLL fusion cDNAs from acute leukaemia RT translocations."; RL Oncogene 8:3157-3160(1993). RN [15] RP PROTEIN SEQUENCE OF 2719-2730, CLEAVAGE, SUBUNIT, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF 2718-ASP--VAL-2720. RX PubMed=12482972; DOI=10.1128/mcb.23.1.186-194.2003; RA Hsieh J.J.-D., Ernst P., Erdjument-Bromage H., Tempst P., Korsmeyer S.J.; RT "Proteolytic cleavage of MLL generates a complex of N- and C-terminal RT fragments that confers protein stability and subnuclear localization."; RL Mol. Cell. Biol. 23:186-194(2003). RN [16] RP CHROMOSOMAL TRANSLOCATION WITH CENPK. RX PubMed=8950979; RA Taki T., Hayashi Y., Taniwaki M., Seto M., Ueda R., Hanada R., Suzukawa K., RA Yokota J., Morishita K.; RT "Fusion of the MLL gene with two different genes, AF-6 and AF-5alpha, by a RT complex translocation involving chromosomes 5, 6, 8 and 11 in infant RT leukemia."; RL Oncogene 13:2121-2130(1996). RN [17] RP CHROMOSOMAL TRANSLOCATION WITH ABI1. RX PubMed=9694699; DOI=10.1182/blood.v92.4.1125; RA Taki T., Shibuya N., Taniwaki M., Hanada R., Morishita K., Bessho F., RA Yanagisawa M., Hayashi Y.; RT "ABI-1, a human homolog to mouse Abl-interactor 1, fuses the MLL gene in RT acute myeloid leukemia with t(10;11)(p11.2;q23)."; RL Blood 92:1125-1130(1998). RN [18] RP INTERACTION WITH SBF1. RX PubMed=9537414; DOI=10.1038/ng0498-331; RA Cui X., De Vivo I., Slany R., Miyamoto A., Firestein R., Cleary M.L.; RT "Association of SET domain and myotubularin-related proteins modulates RT growth control."; RL Nat. Genet. 18:331-337(1998). RN [19] RP INTERACTION WITH PPP1R15A, DISEASE, AND FUNCTION. RX PubMed=10490642; DOI=10.1128/mcb.19.10.7050; RA Adler H.T., Chinery R., Wu D.Y., Kussick S.J., Payne J.M., RA Fornace A.J. Jr., Tkachuk D.C.; RT "Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and RT associate with the GADD34 and hSNF5/INI1 proteins."; RL Mol. Cell. Biol. 19:7050-7060(1999). RN [20] RP CHROMOSOMAL TRANSLOCATION WITH AFF4. RC TISSUE=Placenta; RX PubMed=10588740; DOI=10.1073/pnas.96.25.14535; RA Taki T., Kano H., Taniwaki M., Sako M., Yanagisawa M., Hayashi Y.; RT "AF5q31, a newly identified AF4-related gene, is fused to MLL in infant RT acute lymphoblastic leukemia with ins(5;11)(q31;q13q23)."; RL Proc. Natl. Acad. Sci. U.S.A. 96:14535-14540(1999). RN [21] RP CHROMOSOMAL TRANSLOCATION WITH NCKIPSD/AF3P21. RX PubMed=10648423; DOI=10.1182/blood.v95.3.1066.003k11_1066_1068; RA Sano K., Hayakawa A., Piao J.-H., Kosaka Y., Nakamura H.; RT "Novel SH3 protein encoded by the AF3p21 gene is fused to the mixed lineage RT leukemia protein in a therapy-related leukemia with t(3;11)(p21;q23)."; RL Blood 95:1066-1068(2000). RN [22] RP CHROMOSOMAL TRANSLOCATION WITH GMPS. RX PubMed=11110714; DOI=10.1182/blood.v96.13.4360; RA Pegram L.D., Megonigal M.D., Lange B.J., Nowell P.C., Rowley J.D., RA Rappaport E.F., Felix C.A.; RT "t(3;11) translocation in treatment-related acute myeloid leukemia fuses RT MLL with the GMPS (guanosine 5-prime monophosphate synthetase) gene."; RL Blood 96:4360-4362(2000). RN [23] RP CHROMOSOMAL TRANSLOCATION WITH LPP. RX PubMed=11433529; DOI=10.1002/gcc.1157; RA Daheron L., Veinstein A., Brizard F., Drabkin H., Lacotte L., Guilhot F., RA Larsen C.J., Brizard A., Roche J.; RT "Human LPP gene is fused to MLL in a secondary acute leukemia with a RT t(3;11) (q28;q23)."; RL Genes Chromosomes Cancer 31:382-389(2001). RN [24] RP CHROMOSOMAL TRANSLOCATION WITH TET1. RX PubMed=12124344; RA Ono R., Taki T., Taketani T., Taniwaki M., Kobayashi H., Hayashi Y.; RT "LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in RT acute myeloid leukemia with trilineage dysplasia having RT t(10;11)(q22;q23)."; RL Cancer Res. 62:4075-4080(2002). RN [25] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=12453419; DOI=10.1016/s1097-2765(02)00740-2; RA Nakamura T., Mori T., Tada S., Krajewski W., Rozovskaia T., Wassell R., RA Dubois G., Mazo A., Croce C.M., Canaani E.; RT "ALL-1 is a histone methyltransferase that assembles a supercomplex of RT proteins involved in transcriptional regulation."; RL Mol. Cell 10:1119-1128(2002). RN [26] RP CLEAVAGE, INTERACTION WITH TASP1, AND MUTAGENESIS OF 2666-ASP-GLY-2667 AND RP 2718-ASP--VAL-2720. RX PubMed=14636557; DOI=10.1016/s0092-8674(03)00816-x; RA Hsieh J.J.-D., Cheng E.H.-Y., Korsmeyer S.J.; RT "Taspase1: a threonine aspartase required for cleavage of MLL and proper RT HOX gene expression."; RL Cell 115:293-303(2003). RN [27] RP CHROMOSOMAL TRANSLOCATION WITH ZFYVE19 AND KNL1. RX PubMed=12618766; DOI=10.1038/sj.onc.1206273; RA Chinwalla V., Chien A., Odero M., Neilly M.B., Zeleznik-Le N.J., RA Rowley J.D.; RT "A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene RT MPFYVE on chromosome 15."; RL Oncogene 22:1400-1410(2003). RN [28] RP CHROMOSOMAL TRANSLOCATION WITH KNL1. RX PubMed=12618768; DOI=10.1038/sj.onc.1206272; RA Kuefer M.U., Chinwalla V., Zeleznik-Le N.J., Behm F.G., Naeve C.W., RA Rakestraw K.M., Mukatira S.T., Raimondi S.C., Morris S.W.; RT "Characterization of the MLL partner gene AF15q14 involved in RT t(11;15)(q23;q14)."; RL Oncogene 22:1418-1424(2003). RN [29] RP CHROMOSOMAL TRANSLOCATION WITH DAB2IP. RX PubMed=14978793; DOI=10.1002/gcc.20004; RA von Bergh A.R.M., Wijers P.M., Groot A.J., van Zelderen-Bhola S., RA Falkenburg J.H.F., Kluin P.M., Schuuring E.; RT "Identification of a novel RAS GTPase-activating protein (RASGAP) gene at RT 9q34 as an MLL fusion partner in a patient with de novo acute myeloid RT leukemia."; RL Genes Chromosomes Cancer 39:324-334(2004). RN [30] RP CHROMOSOMAL TRANSLOCATION WITH SEPT11. RX PubMed=14999297; DOI=10.1038/sj.leu.2403334; RA Kojima K., Sakai I., Hasegawa A., Niiya H., Azuma T., Matsuo Y., Fujii N., RA Tanimoto M., Fujita S.; RT "FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line RT CNLBC1 derived from chronic neutrophilic leukemia in transformation with RT t(4;11)(q21;q23)."; RL Leukemia 18:998-1005(2004). RN [31] RP IDENTIFICATION IN THE MLL1/MLL COMPLEX. RX PubMed=15199122; DOI=10.1128/mcb.24.13.5639-5649.2004; RA Yokoyama A., Wang Z., Wysocka J., Sanyal M., Aufiero D.J., Kitabayashi I., RA Herr W., Cleary M.L.; RT "Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase RT complex with menin to regulate Hox gene expression."; RL Mol. Cell. Biol. 24:5639-5649(2004). RN [32] RP CHROMOSOMAL TRANSLOCATION WITH FRYL. RX PubMed=16061630; DOI=10.1158/0008-5472.can-05-1325; RA Hayette S., Cornillet-Lefebvre P., Tigaud I., Struski S., Forissier S., RA Berchet A., Doll D., Gillot L., Brahim W., Delabesse E., Magaud J.-P., RA Rimokh R.; RT "AF4p12, a human homologue to the furry gene of Drosophila, as a novel MLL RT fusion partner."; RL Cancer Res. 65:6521-6525(2005). RN [33] RP FUNCTION, IDENTIFICATION IN THE MLL1/MLL COMPLEX, AND INTERACTION WITH RP KAT8. RX PubMed=15960975; DOI=10.1016/j.cell.2005.04.031; RA Dou Y., Milne T.A., Tackett A.J., Smith E.R., Fukuda A., Wysocka J., RA Allis C.D., Chait B.T., Hess J.L., Roeder R.G.; RT "Physical association and coordinate function of the H3 K4 RT methyltransferase MLL1 and the H4 K16 acetyltransferase MOF."; RL Cell 121:873-885(2005). RN [34] RP DOMAIN 9AATAD. RX PubMed=17467953; DOI=10.1016/j.ygeno.2007.02.003; RA Piskacek S., Gregor M., Nemethova M., Grabner M., Kovarik P., Piskacek M.; RT "Nine-amino-acid transactivation domain: establishment and prediction RT utilities."; RL Genomics 89:756-768(2007). RN [35] RP IDENTIFICATION IN THE MLL1/MLL COMPLEX. RX PubMed=17500065; DOI=10.1074/jbc.m701574200; RA Cho Y.-W., Hong T., Hong S., Guo H., Yu H., Kim D., Guszczynski T., RA Dressler G.R., Copeland T.D., Kalkum M., Ge K.; RT "PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 RT methyltransferase complex."; RL J. Biol. Chem. 282:20395-20406(2007). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-197; SER-518; RP SER-680; THR-840; SER-1056; THR-1845; SER-2098; THR-2147; SER-2151; RP THR-2525; SER-2955; SER-3036; THR-3372 AND SER-3511, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [37] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [38] RP FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF THE MLL1/MLL COMPLEX, RP INTERACTION WITH WDR5, AND MUTAGENESIS OF ASN-3906 AND TYR-3942. RX PubMed=19556245; DOI=10.1074/jbc.m109.014498; RA Patel A., Dharmarajan V., Vought V.E., Cosgrove M.S.; RT "On the mechanism of multiple lysine methylation by the human mixed lineage RT leukemia protein-1 (MLL1) core complex."; RL J. Biol. Chem. 284:24242-24256(2009). RN [39] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1858, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [40] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-2098 AND SER-3515, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [41] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-636; LYS-1130 AND LYS-1235, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [42] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-197; SER-926; RP SER-2955 AND THR-3372, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [43] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2201, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [44] RP IDENTIFICATION IN MLL1 COMPLEX. RX PubMed=23508102; DOI=10.1128/mcb.01742-12; RA van Nuland R., Smits A.H., Pallaki P., Jansen P.W., Vermeulen M., RA Timmers H.T.; RT "Quantitative dissection and stoichiometry determination of the human RT SET1/MLL histone methyltransferase complexes."; RL Mol. Cell. Biol. 33:2067-2077(2013). RN [45] RP SUBCELLULAR LOCATION. RX PubMed=25593309; DOI=10.1101/gad.252189.114; RA Gong F., Chiu L.Y., Cox B., Aymard F., Clouaire T., Leung J.W., RA Cammarata M., Perez M., Agarwal P., Brodbelt J.S., Legube G., Miller K.M.; RT "Screen identifies bromodomain protein ZMYND8 in chromatin recognition of RT transcription-associated DNA damage that promotes homologous RT recombination."; RL Genes Dev. 29:197-211(2015). RN [46] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF ASN-3906. RX PubMed=25561738; DOI=10.1074/jbc.m114.627646; RA Shinsky S.A., Monteith K.E., Viggiano S., Cosgrove M.S.; RT "Biochemical reconstitution and phylogenetic comparison of human SET1 RT family core complexes involved in histone methylation."; RL J. Biol. Chem. 290:6361-6375(2015). RN [47] RP INVOLVEMENT IN WDSTS. RX PubMed=22795537; DOI=10.1016/j.ajhg.2012.06.008; RA Jones W.D., Dafou D., McEntagart M., Woollard W.J., Elmslie F.V., RA Holder-Espinasse M., Irving M., Saggar A.K., Smithson S., Trembath R.C., RA Deshpande C., Simpson M.A.; RT "De novo mutations in MLL cause Wiedemann-Steiner syndrome."; RL Am. J. Hum. Genet. 91:358-364(2012). RN [48] RP INTERACTION WITH ZNF335. RX PubMed=23178126; DOI=10.1016/j.cell.2012.10.043; RA Yang Y.J., Baltus A.E., Mathew R.S., Murphy E.A., Evrony G.D., RA Gonzalez D.M., Wang E.P., Marshall-Walker C.A., Barry B.J., Murn J., RA Tatarakis A., Mahajan M.A., Samuels H.H., Shi Y., Golden J.A., Mahajnah M., RA Shenhav R., Walsh C.A.; RT "Microcephaly gene links trithorax and REST/NRSF to control neural stem RT cell proliferation and differentiation."; RL Cell 151:1097-1112(2012). RN [49] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1858; SER-2098; THR-2525; RP SER-2611; SER-2796; SER-2955; SER-3036; SER-3511 AND SER-3527, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [50] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, METHYLATION AT RP CYS-3882, AND MUTAGENESIS OF CYS-3882. RX PubMed=24235145; DOI=10.1074/jbc.m113.501064; RA Patel A., Vought V.E., Swatkoski S., Viggiano S., Howard B., RA Dharmarajan V., Monteith K.E., Kupakuwana G., Namitz K.E., Shinsky S.A., RA Cotter R.J., Cosgrove M.S.; RT "Automethylation activities within the mixed lineage leukemia-1 (MLL1) core RT complex reveal evidence supporting a 'two-active site' model for multiple RT histone H3 lysine 4 methylation."; RL J. Biol. Chem. 289:868-884(2014). RN [51] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1837, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [52] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-2528, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [53] RP INTERACTION WITH HUMAN HERPESVIRUS 8/HHV-8 PROTEIN LANA1, AND SUBCELLULAR RP LOCATION. RX PubMed=34850113; DOI=10.1093/nar/gkab1094; RA Tan M., Li S., Juillard F., Chitas R., Custodio T.F., Xue H., Szymula A., RA Sun Q., Liu B., Alvarez A.L., Chen S., Huang J., Simas J.P., McVey C.E., RA Kaye K.M.; RT "MLL1 is regulated by KSHV LANA and is important for virus latency."; RL Nucleic Acids Res. 49:12895-12911(2021). RN [54] RP STRUCTURE BY NMR OF 1146-1214 IN COMPLEX WITH ZINC, DOMAIN CXXC-TYPE RP ZINC-FINGER, DNA-BINDING, AND MUTAGENESIS OF ARG-1151; ARG-1153; ARG-1154; RP CYS-1155; CYS-1158; CYS-1161; GLN-1162; ASP-1166; CYS-1167; CYS-1170; RP ASN-1172; CYS-1173; ASP-1175; LYS-1176; 1178-LYS--GLY-1181; LYS-1178; RP PHE-1179; ASN-1183; LYS-1185; LYS-1186; GLN-1187; CYS-1188; CYS-1189; RP ARG-1192; LYS-1193; CYS-1194; GLN-1195 AND ASN-1196. RX PubMed=16990798; DOI=10.1038/sj.emboj.7601340; RA Allen M.D., Grummitt C.G., Hilcenko C., Min S.Y., Tonkin L.M., RA Johnson C.M., Freund S.M., Bycroft M., Warren A.J.; RT "Solution structure of the nonmethyl-CpG-binding CXXC domain of the RT leukaemia-associated MLL histone methyltransferase."; RL EMBO J. 25:4503-4512(2006). RN [55] RP STRUCTURE BY NMR OF 2842-2869 IN COMPLEX WITH CREBBP. RX PubMed=16253272; DOI=10.1016/j.jmb.2005.09.059; RA De Guzman R.N., Goto N.K., Dyson H.J., Wright P.E.; RT "Structural basis for cooperative transcription factor binding to the CBP RT coactivator."; RL J. Mol. Biol. 355:1005-1013(2006). RN [56] {ECO:0007744|PDB:2JYI} RP STRUCTURE BY NMR OF 1147-1203. RA Cierpicki T., Riesbeck L.E., Grembecka J., Lukasik S.M., Omonkowska M., RA Shultis D., Zeleznik-Le N.J., Bushweller J.H.; RT "Structural basis for maintenance of unmethylated CpG elements by the CXXC RT domain of MLL and its critical contributions to MLL-AF9 immortalization RT activity."; RL Submitted (DEC-2007) to the PDB data bank. RN [57] RP X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 3764-3776 IN COMPLEX WITH WDR5, RP AND INTERACTION WITH WDR5. RX PubMed=18829459; DOI=10.1074/jbc.c800164200; RA Patel A., Dharmarajan V., Cosgrove M.S.; RT "Structure of WDR5 bound to mixed lineage leukemia protein-1 peptide."; RL J. Biol. Chem. 283:32158-32161(2008). RN [58] {ECO:0007744|PDB:3EMH} RP X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 3764-3776 IN COMPLEX WITH WDR5, RP INTERACTION WITH WDR5, AND MUTAGENESIS OF ARG-3765 AND HIS-3769. RX PubMed=18840606; DOI=10.1074/jbc.m806900200; RA Song J.J., Kingston R.E.; RT "WDR5 interacts with mixed lineage leukemia (MLL) protein via the histone RT H3-binding pocket."; RL J. Biol. Chem. 283:35258-35264(2008). RN [59] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 3785-3969 IN COMPLEX WITH ZINC; RP S-ADENOSYL-L-HOMOCYSTEINE AND HISTONE H3 PEPTIDE, FUNCTION, CATALYTIC RP ACTIVITY, DOMAIN SET, INTERACTION WITH ASH2L AND RBBP5, AND MUTAGENESIS OF RP TYR-3858; GLN-3867; ASP-3869; ARG-3871; GLU-3872; TYR-3874; LYS-3878 AND RP TYR-3942. RX PubMed=19187761; DOI=10.1016/j.molcel.2008.12.029; RA Southall S.M., Wong P.S., Odho Z., Roe S.M., Wilson J.R.; RT "Structural basis for the requirement of additional factors for MLL1 SET RT domain activity and recognition of epigenetic marks."; RL Mol. Cell 33:181-191(2009). RN [60] {ECO:0007744|PDB:2KYU} RP STRUCTURE BY NMR OF 1564-1628 IN COMPLEX WITH ZINC, FUNCTION, DOMAIN, RP MUTAGENESIS OF TRP-1594; VAL-1617 AND TYR-1619, AND INTERACTION WITH PPIE. RX PubMed=20677832; DOI=10.1021/bi1009387; RA Park S., Osmers U., Raman G., Schwantes R.H., Diaz M.O., Bushweller J.H.; RT "The PHD3 domain of MLL acts as a CYP33-regulated switch between MLL- RT mediated activation and repression."; RL Biochemistry 49:6576-6586(2010). RN [61] {ECO:0007744|PDB:2KU7, ECO:0007744|PDB:3LQH, ECO:0007744|PDB:3LQI, ECO:0007744|PDB:3LQJ} RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 1566-1784 IN COMPLEX WITH ZINC RP AND METHYLATED HISTONE H3, INTERACTION WITH PPIE, DOMAIN, AND MUTAGENESIS RP OF TYR-1581; GLN-1587 AND TRP-1594. RX PubMed=20541251; DOI=10.1016/j.cell.2010.05.016; RA Wang Z., Song J., Milne T.A., Wang G.G., Li H., Allis C.D., Patel D.J.; RT "Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to RT CyP33 and HDAC-mediated repression."; RL Cell 141:1183-1194(2010). RN [62] {ECO:0007744|PDB:2KKF} RP STRUCTURE BY NMR OF 1147-1203 IN COMPLEX WITH ZINC AND TARGET DNA, RP FUNCTION, DOMAIN CXXC-TYPE ZINC-FINGER, AND MUTAGENESIS OF ARG-1150; RP ARG-1154; LYS-1185; GLN-1187; CYS-1188; LYS-1193; LEU-1197 AND MET-1200. RX PubMed=20010842; DOI=10.1038/nsmb.1714; RA Cierpicki T., Risner L.E., Grembecka J., Lukasik S.M., Popovic R., RA Omonkowska M., Shultis D.D., Zeleznik-Le N.J., Bushweller J.H.; RT "Structure of the MLL CXXC domain-DNA complex and its functional role in RT MLL-AF9 leukemia."; RL Nat. Struct. Mol. Biol. 17:62-68(2010). RN [63] {ECO:0007744|PDB:3P4F} RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 3761-3770 IN COMPLEX WITH RBBP5 RP AND WDR5, AND FUNCTION. RX PubMed=21220120; DOI=10.1016/j.str.2010.09.022; RA Avdic V., Zhang P., Lanouette S., Groulx A., Tremblay V., Brunzelle J., RA Couture J.F.; RT "Structural and biochemical insights into MLL1 core complex assembly."; RL Structure 19:101-108(2011). RN [64] {ECO:0007744|PDB:4GQ6} RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 6-15 IN COMPLEX WITH MEN1, RP INTERACTION WITH MEN1, AND INTERACTION OF FUSION PROTEIN KMT2A-MLLT3 WITH RP MEN1. RX PubMed=22936661; DOI=10.1182/blood-2012-05-429274; RA Shi A., Murai M.J., He S., Lund G., Hartley T., Purohit T., Reddy G., RA Chruszcz M., Grembecka J., Cierpicki T.; RT "Structural insights into inhibition of the bivalent menin-MLL interaction RT by small molecules in leukemia."; RL Blood 120:4461-4469(2012). RN [65] {ECO:0007744|PDB:4ESG} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 3755-3771 IN COMPLEX WITH WDR5, RP INTERACTION WITH THE WRAD COMPLEX, INTERACTION WITH WDR5, MUTAGENESIS OF RP SER-3763; ARG-3765 AND HIS-3769, AND MOTIF WIN. RX PubMed=22665483; DOI=10.1074/jbc.m112.364125; RA Dharmarajan V., Lee J.H., Patel A., Skalnik D.G., Cosgrove M.S.; RT "Structural basis for WDR5 interaction (Win) motif recognition in human RT SET1 family histone methyltransferases."; RL J. Biol. Chem. 287:27275-27289(2012). RN [66] {ECO:0007744|PDB:3U85, ECO:0007744|PDB:3U88} RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 6-25 AND 103-153 IN COMPLEX WITH RP MEN1 AND PSIP1, INTERACTION WITH MEN1, INTERACTION OF KMT2A-MEN1 COMPLEX RP WITH PSIP1, MOTIF MBM, AND MUTAGENESIS OF ARG-6; TRP-7; ARG-8; PHE-9; RP PRO-10; ALA-11; ARG-12; PRO-13; ARG-24 AND ARG-25. RX PubMed=22327296; DOI=10.1038/nature10806; RA Huang J., Gurung B., Wan B., Matkar S., Veniaminova N.A., Wan K., RA Merchant J.L., Hua X., Lei M.; RT "The same pocket in menin binds both MLL and JUND but has opposite effects RT on transcription."; RL Nature 482:542-546(2012). RN [67] {ECO:0007744|PDB:2LXS, ECO:0007744|PDB:2LXT} RP STRUCTURE BY NMR OF 2840-2858 IN COMPLEX WITH CREBBP AND CREB1. RX PubMed=23651431; DOI=10.1021/cb4002188; RA Bruschweiler S., Konrat R., Tollinger M.; RT "Allosteric communication in the KIX domain proceeds through dynamic RT repacking of the hydrophobic core."; RL ACS Chem. Biol. 8:1600-1610(2013). RN [68] {ECO:0007744|PDB:2MTN} RP STRUCTURE BY NMR OF 110-160 IN COMPLEX WITH PSIP1, DOMAIN IBM MOTIF, RP INTERACTION WITH PSIP1 AND MEN1, INTERACTION OF FUSION PROTEIN KMT2A-MLLT3 RP WITH PSIP1 AND MEN1, AND MUTAGENESIS OF PHE-129; PHE-148 AND LEU-149. RX PubMed=25305204; DOI=10.1182/blood-2014-01-550079; RA Murai M.J., Pollock J., He S., Miao H., Purohit T., Yokom A., Hess J.L., RA Muntean A.G., Grembecka J., Cierpicki T.; RT "The same site on the integrase-binding domain of lens epithelium-derived RT growth factor is a therapeutic target for MLL leukemia and HIV."; RL Blood 124:3730-3737(2014). RN [69] {ECO:0007744|PDB:2MSR} RP STRUCTURE BY NMR OF 140-160 IN COMPLEX WITH PSIP1, INTERACTION WITH PSIP1, RP AND MUTAGENESIS OF PHE-129; PHE-133; GLU-144; GLU-146; PHE-148 AND PHE-151. RX PubMed=25082813; DOI=10.1158/0008-5472.can-13-3602; RA Cermakova K., Tesina P., Demeulemeester J., El Ashkar S., Mereau H., RA Schwaller J., Rezacova P., Veverka V., De Rijck J.; RT "Validation and structural characterization of the LEDGF/p75-MLL interface RT as a new target for the treatment of MLL-dependent leukemia."; RL Cancer Res. 74:5139-5151(2014). RN [70] {ECO:0007744|PDB:5F5E, ECO:0007744|PDB:5F6L} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 3813-3969 IN COMPLEX WITH RP S-ADENOSYL-L-HOMOCYSTEINE AND ZINC, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, RP DOMAIN, AND MUTAGENESIS OF ASN-3861; ARG-3864 AND GLN-3867. RX PubMed=26886794; DOI=10.1038/nature16952; RA Li Y., Han J., Zhang Y., Cao F., Liu Z., Li S., Wu J., Hu C., Wang Y., RA Shuai J., Chen J., Cao L., Li D., Shi P., Tian C., Zhang J., Dou Y., Li G., RA Chen Y., Lei M.; RT "Structural basis for activity regulation of MLL family RT methyltransferases."; RL Nature 530:447-452(2016). RN [71] {ECO:0007744|PDB:5SVH} RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 2839-2869. RA Langelaan D.N., Smith S.P.; RT "Design of a nanomolar affinity ligand to the KIX domain of CBP."; RL Submitted (AUG-2016) to the PDB data bank. RN [72] {ECO:0007744|PDB:6EMQ} RP STRUCTURE BY NMR OF 111-160 IN COMPLEX WITH PSIP1, INTERACTION WITH PSIP1, RP DOMAIN IBM MOTIF, MUTAGENESIS OF VAL-132; PHE-133; SER-136 AND SER-142, AND RP PHOSPHORYLATION AT SER-136; SER-142 AND SER-153. RX PubMed=29997176; DOI=10.1073/pnas.1803909115; RA Sharma S., Cermakova K., De Rijck J., Demeulemeester J., Fabry M., RA El Ashkar S., Van Belle S., Lepsik M., Tesina P., Duchoslav V., Novak P., RA Hubalek M., Srb P., Christ F., Rezacova P., Hodges H.C., Debyser Z., RA Veverka V.; RT "Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase- RT dependent phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 115:E7053-E7062(2018). RN [73] {ECO:0007744|PDB:4NW3} RP X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF 1147-1204 IN COMPLEX WITH CPG RP DNA, DOMAIN CXXC-TYPE ZINC-FINGER, AND ZINC-BINDING. RX PubMed=29276034; DOI=10.1016/j.str.2017.11.022; RA Xu C., Liu K., Lei M., Yang A., Li Y., Hughes T.R., Min J.; RT "DNA Sequence Recognition of Human CXXC Domains and Their Structural RT Determinants."; RL Structure 26:85-95.e3(2018). CC -!- FUNCTION: Histone methyltransferase that plays an essential role in CC early development and hematopoiesis (PubMed:12453419, PubMed:15960975, CC PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, CC PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a CC multiprotein complex that mediates both methylation of 'Lys-4' of CC histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 CC (H4K16ac) (PubMed:12453419, PubMed:15960975, PubMed:19187761, CC PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:24235145, CC PubMed:26886794). Catalyzes methyl group transfer from S-adenosyl-L- CC methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) CC via a non-processive mechanism. Part of chromatin remodeling machinery CC predominantly forms H3K4me1 and H3K4me2 methylation marks at active CC chromatin sites where transcription and DNA repair take place CC (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, CC PubMed:20677832, PubMed:21220120, PubMed:25561738, PubMed:26886794). CC Has weak methyltransferase activity by itself, and requires other CC component of the MLL1/MLL complex to obtain full methyltransferase CC activity (PubMed:19187761, PubMed:26886794). Has no activity toward CC histone H3 phosphorylated on 'Thr-3', less activity toward H3 CC dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward CC H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG CC elements in the promoter of target genes and helps maintain them in the CC nonmethylated state (PubMed:20010842). Required for transcriptional CC activation of HOXA9 (PubMed:12453419, PubMed:20010842, CC PubMed:20677832). Promotes PPP1R15A-induced apoptosis CC (PubMed:10490642). Plays a critical role in the control of circadian CC gene expression and is essential for the transcriptional activation CC mediated by the CLOCK-BMAL1 heterodimer (By similarity). Establishes a CC permissive chromatin state for circadian transcription by mediating a CC rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone CC modification directs the circadian acetylation at H3K9 and H3K14 CC allowing the recruitment of CLOCK-BMAL1 to chromatin (By similarity). CC Also has auto-methylation activity on Cys-3882 in absence of histone H3 CC substrate (PubMed:24235145). {ECO:0000250|UniProtKB:P55200, CC ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, CC ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19187761, CC ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20010842, CC ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:24235145, CC ECO:0000269|PubMed:26886794, ECO:0000305|PubMed:20677832}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = N(6)- CC methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine + H(+); CC Xref=Rhea:RHEA:60264, Rhea:RHEA-COMP:15543, Rhea:RHEA-COMP:15547, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.364; CC Evidence={ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:19187761, CC ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:24235145, CC ECO:0000269|PubMed:25561738, ECO:0000269|PubMed:26886794}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60265; CC Evidence={ECO:0000305|PubMed:19556245, ECO:0000305|PubMed:25561738}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine CC = N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L- CC homocysteine + H(+); Xref=Rhea:RHEA:60268, Rhea:RHEA-COMP:15540, CC Rhea:RHEA-COMP:15543, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929, ChEBI:CHEBI:61976; CC Evidence={ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:24235145, CC ECO:0000269|PubMed:25561738, ECO:0000269|PubMed:26886794}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60269; CC Evidence={ECO:0000305|PubMed:25561738}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-cysteinyl-[protein] + S-adenosyl-L-methionine = S-methyl-L- CC cysteinyl-[protein] + S-adenosyl-L-homocysteine + H(+); CC Xref=Rhea:RHEA:66544, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:10132, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:82612; CC Evidence={ECO:0000269|PubMed:24235145}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66545; CC Evidence={ECO:0000269|PubMed:24235145}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=10.4 uM for S-adenosyl-L-methionine (for histone-lysine CC N-methyltransferase activity) {ECO:0000269|PubMed:24235145}; CC KM=6.5 uM for S-adenosyl-L-methionine (for protein-cysteine CC methyltransferase) {ECO:0000269|PubMed:24235145}; CC -!- SUBUNIT: MLL cleavage product N320 heterodimerizes with MLL cleavage CC product C180 (via SET and FYRC domains). Component of some MLL1/MLL CC complex, at least composed of the core components KMT2A/MLL1, ASH2L, CC HCFC1/HCF1, HCFC2, WDR5, DPY30 and RBBP5, as well as the facultative CC components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, CC MEN1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, CC RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 CC (PubMed:15199122, PubMed:15960975, PubMed:17500065, PubMed:19187761, CC PubMed:19556245, PubMed:23508102, PubMed:26886794). Forms a core CC complex with the evolutionary conserved subcomplex WRAD composed of CC WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits; WRAD differentially CC stimulates the methyltransferase activity (PubMed:25561738). Interacts CC (via WIN motif) with WDR5; the interaction is direct (PubMed:18829459, CC PubMed:18840606, PubMed:19556245, PubMed:22665483). Interaction with CC WDR5 is required for stable interaction with ASH2L and RBBP5, and CC thereby also for optimal histone methyltransferase activity CC (PubMed:26886794). Interacts with KAT8/MOF; the interaction is direct CC (PubMed:15960975). Interacts with SBF1 and PPP1R15A (PubMed:10490642, CC PubMed:9537414). Interacts with ZNF335 (PubMed:23178126). Interacts CC with CLOCK and BMAL1 in a circadian manner (By similarity). Interacts CC with PPIE; this results in decreased histone H3 methyltransferase CC activity (PubMed:20541251, PubMed:20677832). Interacts with CREBBP CC (PubMed:16253272). Interacts with the WRAD complex composed of WDR5, CC RBBP5, ASH2L and DPY30 (PubMed:22665483). Interacts (via MBM motif) CC with MEN1 (PubMed:22327296, PubMed:22936661, PubMed:25305204). CC Interacts (via IBM motifs) with PSIP1 (via IBD domain) with moderate CC affinity whereas the KMT2A-MEN1 complex interacts with a greater CC affinity; MEN1 enhances interaction of KMT2A with PSIP1 CC (PubMed:22327296, PubMed:25082813, PubMed:25305204, PubMed:29997176). CC Phosphorylation increases its affinity for PSIP1 (PubMed:29997176). CC Forms a complex with CREBBP and CREB1 (PubMed:23651431). CC {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, CC ECO:0000269|PubMed:12482972, ECO:0000269|PubMed:14636557, CC ECO:0000269|PubMed:15199122, ECO:0000269|PubMed:15960975, CC ECO:0000269|PubMed:16253272, ECO:0000269|PubMed:16990798, CC ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:18829459, CC ECO:0000269|PubMed:18840606, ECO:0000269|PubMed:19187761, CC ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20541251, CC ECO:0000269|PubMed:20677832, ECO:0000269|PubMed:21220120, CC ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22665483, CC ECO:0000269|PubMed:23178126, ECO:0000269|PubMed:23651431, CC ECO:0000269|PubMed:25082813, ECO:0000269|PubMed:25305204, CC ECO:0000269|PubMed:25561738, ECO:0000269|PubMed:26886794, CC ECO:0000269|PubMed:29997176, ECO:0000269|PubMed:9537414}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes virus 8/HHV-8 CC protein LANA1; this interaction regulates the MLL1 histone CC methyltransferase activity on viral DNA. {ECO:0000269|PubMed:34850113}. CC -!- INTERACTION: CC Q03164; P10275: AR; NbExp=4; IntAct=EBI-591370, EBI-608057; CC Q03164; Q9UBL3-3: ASH2L; NbExp=4; IntAct=EBI-591370, EBI-16130425; CC Q03164; Q6P1J9: CDC73; NbExp=4; IntAct=EBI-591370, EBI-930143; CC Q03164; Q6PD62: CTR9; NbExp=5; IntAct=EBI-591370, EBI-1019583; CC Q03164; P68431: H3C12; NbExp=11; IntAct=EBI-591370, EBI-79722; CC Q03164; Q9H7Z6: KAT8; NbExp=3; IntAct=EBI-591370, EBI-896414; CC Q03164; Q03164: KMT2A; NbExp=5; IntAct=EBI-591370, EBI-591370; CC Q03164; O00255-2: MEN1; NbExp=12; IntAct=EBI-591370, EBI-9869387; CC Q03164; Q8N7H5: PAF1; NbExp=4; IntAct=EBI-591370, EBI-2607770; CC Q03164; Q9UNP9: PPIE; NbExp=4; IntAct=EBI-591370, EBI-591818; CC Q03164; Q15291: RBBP5; NbExp=12; IntAct=EBI-591370, EBI-592823; CC Q03164; P26373: RPL13; NbExp=2; IntAct=EBI-591370, EBI-356849; CC Q03164; Q96EB6: SIRT1; NbExp=5; IntAct=EBI-591370, EBI-1802965; CC Q03164; Q13309-1: SKP2; NbExp=2; IntAct=EBI-591370, EBI-15490084; CC Q03164; P61964: WDR5; NbExp=17; IntAct=EBI-591370, EBI-540834; CC Q03164; Q9WTL8: Bmal1; Xeno; NbExp=3; IntAct=EBI-591370, EBI-644534; CC Q03164; O08785: Clock; Xeno; NbExp=3; IntAct=EBI-591370, EBI-79859; CC Q03164; P45481: Crebbp; Xeno; NbExp=7; IntAct=EBI-591370, EBI-296306; CC PRO_0000390949; Q02548: PAX5; NbExp=2; IntAct=EBI-2610266, EBI-296331; CC PRO_0000390950; Q92794: KAT6A; NbExp=10; IntAct=EBI-2638616, EBI-948013; CC PRO_0000390950; P61964: WDR5; NbExp=2; IntAct=EBI-2638616, EBI-540834; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12482972, CC ECO:0000269|PubMed:25593309, ECO:0000269|PubMed:34850113}. CC -!- SUBCELLULAR LOCATION: [MLL cleavage product N320]: Nucleus. CC -!- SUBCELLULAR LOCATION: [MLL cleavage product C180]: Nucleus. CC Note=Localizes to a diffuse nuclear pattern when not associated with CC MLL cleavage product N320. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q03164-1; Sequence=Displayed; CC Name=2; Synonyms=14P-18B; CC IsoId=Q03164-2; Sequence=VSP_006666; CC Name=3; CC IsoId=Q03164-3; Sequence=VSP_046879; CC -!- TISSUE SPECIFICITY: Heart, lung, brain and T- and B-lymphocytes. CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large CC number of yeast and animal transcription factors. CC {ECO:0000269|PubMed:17467953}. CC -!- DOMAIN: The SET domain structure is atypical and is not in an optimal CC position to have methyltransferase activity. It requires other CC components of the MLL1/MLL complex, such as ASH2L or RBBP5, to order CC the active site and obtain optimal histone methyltransferase activity. CC {ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:26886794}. CC -!- DOMAIN: The CXXC-type zinc finger binds to DNA sequence elements CC containing unnmethylated CpG dinucleotides. CC {ECO:0000269|PubMed:16990798, ECO:0000269|PubMed:20010842, CC ECO:0000269|PubMed:29276034}. CC -!- DOMAIN: The third PHD-type zinc-finger binds both trimethylated histone CC H3K4me3 and PPIE; histone and PPIE bind to distinct surfaces CC (PubMed:20541251, PubMed:20677832). Nevertheless, PPIE binding and CC histone binding are mutually inhibitory (PubMed:20677832). CC Isomerization of a peptidylproline bond in the linker between the third CC PHD-type zinc-finger and the bromo domain disrupts the interaction CC between the bromo domain and the third PHD-type zinc-finger, and CC thereby facilitates interaction with PPIE (PubMed:20541251). CC {ECO:0000269|PubMed:20541251, ECO:0000269|PubMed:20677832}. CC -!- PTM: Proteolytic cleavage by TASP1 generates MLL cleavage product N320 CC and MLL cleavage product C180, which reassemble through a non-covalent CC association. 2 cleavage sites exist, cleavage site 1 (CS1) and cleavage CC site 2 (CS2), to generate MLL cleavage products N320 and C180. CS2 is CC the major site. {ECO:0000269|PubMed:12482972, CC ECO:0000269|PubMed:14636557}. CC -!- PTM: Phosphorylation increases its interaction with PSIP1. CC {ECO:0000269|PubMed:29997176}. CC -!- PTM: Auto-methylated at Cys-3882: auto-methylation is inhibited by the CC WRAD complex and unmodified histone H3. {ECO:0000269|PubMed:24235145}. CC -!- DISEASE: Wiedemann-Steiner syndrome (WDSTS) [MIM:605130]: A syndrome CC characterized by hairy elbows (hypertrichosis cubiti), intellectual CC disability, a distinctive facial appearance, and short stature. Facial CC characteristics include long eyelashes, thick or arched eyebrows with a CC lateral flare, and downslanting and vertically narrow palpebral CC fissures. {ECO:0000269|PubMed:22795537}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Note=Chromosomal aberrations involving KMT2A are a cause of CC acute leukemias. Translocation t(1;11)(q21;q23) with MLLT11/AF1Q; CC translocation t(3;11)(p21;q23) with NCKIPSD/AF3p21; translocation CC t(3,11)(q25,q23) with GMPS; translocation t(4;11)(q21;q23) with CC AFF1/MLLT2/AF4; insertion ins(5;11)(q31;q13q23) with AFF4/AF5Q31; CC translocation t(5;11)(q12;q23) with AF5-alpha/CENPK; translocation CC t(6;11)(q27;q23) with AFDN; translocation t(9;11)(p22;q23) with CC MLLT3/AF9; translocation t(10;11)(p11.2;q23) with ABI1; translocation CC t(10;11)(p12;q23) with MLLT10/AF10; t(11;15)(q23;q14) with KNL1 and CC ZFYVE19; translocation t(11;17)(q23;q21) with MLLT6/AF17; translocation CC t(11;19)(q23;p13.3) with ELL; translocation t(11;19)(q23;p13.3) with CC MLLT1/ENL; translocation t(11;19)(q23;p23) with GAS7; translocation CC t(X;11)(q13;q23) with FOXO4/AFX1. Translocation t(3;11)(q28;q23) with CC LPP. Translocation t(10;11)(q22;q23) with TET1. Translocation CC t(9;11)(q34;q23) with DAB2IP. Translocation t(4;11)(p12;q23) with FRYL. CC Fusion proteins KMT2A-MLLT1, KMT2A-MLLT3 and KMT2A-ELL interact with CC PPP1R15A and, on the contrary to unfused KMT2A, inhibit PPP1R15A- CC induced apoptosis. Fusion protein KMT2A-MLLT3 interacts with MEN1 and CC PSIP1 (PubMed:22936661, PubMed:25305204). {ECO:0000269|PubMed:10490642, CC ECO:0000269|PubMed:22936661, ECO:0000269|PubMed:25305204}. CC -!- DISEASE: Note=A chromosomal aberration involving KMT2A may be a cause CC of chronic neutrophilic leukemia. Translocation t(4;11)(q21;q23) with CC SEPT11. {ECO:0000269|PubMed:10490642}. CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase CC superfamily. Histone-lysine methyltransferase family. TRX/MLL CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA58669.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAG26332.2; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=BAD92745.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/13/kmt2a"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L04284; AAA58669.1; ALT_FRAME; mRNA. DR EMBL; Z69744; CAA93625.1; -; Genomic_DNA. DR EMBL; Z69745; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69746; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69747; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69748; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69749; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69750; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69751; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69752; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69753; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69754; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69755; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69756; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69757; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69758; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69759; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69760; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69761; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69762; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69763; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69764; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69765; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69766; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69767; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69768; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69769; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69770; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69772; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69773; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69774; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69775; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69776; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69777; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69778; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69779; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; Z69780; CAA93625.1; JOINED; Genomic_DNA. DR EMBL; AY373585; AAQ63624.1; -; Genomic_DNA. DR EMBL; AP000941; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP001267; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; D14540; BAA03407.1; -; mRNA. DR EMBL; AB209508; BAD92745.1; ALT_FRAME; mRNA. DR EMBL; L04731; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; L01986; AAA92511.1; -; mRNA. DR EMBL; X83604; CAA58584.1; -; Genomic_DNA. DR EMBL; S78570; AAB34770.1; -; mRNA. DR EMBL; U04737; AAA18644.1; -; Genomic_DNA. DR EMBL; S66432; AAB28545.1; -; mRNA. DR EMBL; AF232001; AAG26335.2; -; mRNA. DR EMBL; AF231998; AAG26332.2; ALT_SEQ; mRNA. DR CCDS; CCDS31686.1; -. [Q03164-1] DR CCDS; CCDS55791.1; -. [Q03164-3] DR PIR; A44265; A44265. DR PIR; I52578; I52578. DR PIR; I53035; I53035. DR RefSeq; NP_001184033.1; NM_001197104.2. [Q03164-3] DR RefSeq; NP_005924.2; NM_005933.4. [Q03164-1] DR PDB; 2AGH; NMR; -; C=2839-2869. DR PDB; 2J2S; NMR; -; A=1143-1214. DR PDB; 2JYI; NMR; -; A=1147-1203. DR PDB; 2KKF; NMR; -; A=1147-1203. DR PDB; 2KU7; NMR; -; A=1585-1628. DR PDB; 2KYU; NMR; -; A=1564-1628. DR PDB; 2LXS; NMR; -; B=2840-2858. DR PDB; 2LXT; NMR; -; B=2840-2858. DR PDB; 2MSR; NMR; -; A=140-160. DR PDB; 2MTN; NMR; -; A=110-160. DR PDB; 2W5Y; X-ray; 2.00 A; A=3785-3969. DR PDB; 2W5Z; X-ray; 2.20 A; A=3785-3969. DR PDB; 3EG6; X-ray; 1.72 A; C=3762-3773. DR PDB; 3EMH; X-ray; 1.37 A; B=3764-3776. DR PDB; 3LQH; X-ray; 1.72 A; A=1566-1784. DR PDB; 3LQI; X-ray; 1.92 A; A/B/C=1566-1784. DR PDB; 3LQJ; X-ray; 1.90 A; A/B=1566-1784. DR PDB; 3P4F; X-ray; 2.35 A; C=3761-3770. DR PDB; 3U85; X-ray; 3.00 A; B=6-25. DR PDB; 3U88; X-ray; 3.00 A; M/N=103-153. DR PDB; 4ESG; X-ray; 1.70 A; C/D=3755-3771. DR PDB; 4GQ6; X-ray; 1.55 A; B=6-15. DR PDB; 4NW3; X-ray; 2.82 A; A=1147-1204. DR PDB; 5F5E; X-ray; 1.80 A; A=3813-3969. DR PDB; 5F6L; X-ray; 1.90 A; A=3813-3969. DR PDB; 5SVH; X-ray; 2.05 A; B=2839-2869. DR PDB; 6EMQ; NMR; -; A=111-160. DR PDB; 6KIU; EM; 3.20 A; K=3754-3969. DR PDB; 6KIV; EM; 4.00 A; K=3754-3969. DR PDB; 6KIX; EM; 4.10 A; K=3754-3969. DR PDB; 6KIZ; EM; 4.50 A; K=3754-3969. DR PDB; 6PWV; EM; 6.20 A; C=3762-3969. DR PDB; 6PWW; EM; 4.40 A; C=3762-3969. DR PDB; 6U9K; X-ray; 2.00 A; A/B=3813-3969. DR PDB; 6U9M; X-ray; 2.05 A; A/B=3813-3969. DR PDB; 6U9N; X-ray; 1.95 A; A/B=3813-3969. DR PDB; 6U9R; X-ray; 2.10 A; A/B=3813-3969. DR PDB; 6W5I; EM; 6.90 A; C=3762-3969. DR PDB; 6W5M; EM; 4.60 A; C=3762-3969. DR PDB; 6W5N; EM; 6.00 A; C=3762-3969. DR PDB; 7MBM; EM; -; C=3762-3969. DR PDB; 7MBN; EM; -; C=3762-3969. DR PDB; 7RZD; X-ray; 1.82 A; C=747-755. DR PDB; 7RZJ; X-ray; 1.80 A; E=747-755. DR PDB; 7S79; X-ray; 1.53 A; E=747-755. DR PDB; 7S7D; X-ray; 1.56 A; E=747-755. DR PDB; 7S8A; X-ray; 2.10 A; C=747-755. DR PDB; 7S8E; X-ray; 1.60 A; E=747-755. DR PDB; 7S8F; X-ray; 1.80 A; C=747-755. DR PDB; 7U5V; X-ray; 2.59 A; A=3811-3969. DR PDB; 7W67; X-ray; 2.19 A; C=3813-3969. DR PDB; 7W6A; X-ray; 2.21 A; C=3813-3969. DR PDB; 7W6I; X-ray; 2.56 A; C=3813-3969. DR PDB; 7W6J; X-ray; 2.68 A; C=3813-3969. DR PDB; 7ZEY; NMR; -; B=1564-1627. DR PDB; 7ZEZ; NMR; -; B=1564-1627. DR PDB; 9C4S; X-ray; 1.54 A; B=4-15. DR PDB; 9C4T; X-ray; 1.46 A; B=4-15. DR PDB; 9C4U; X-ray; 1.57 A; B=4-15. DR PDB; 9C4V; X-ray; 1.47 A; B=4-15. DR BMRB; Q03164; -. DR EMDB; EMD-0694; -. DR EMDB; EMD-0695; -. DR EMDB; EMD-20512; -. DR EMDB; EMD-20513; -. DR EMDB; EMD-21542; -. DR EMDB; EMD-21543; -. DR EMDB; EMD-21544; -. DR EMDB; EMD-23738; -. DR EMDB; EMD-23739; -. DR EMDB; EMD-9998; -. DR EMDB; EMD-9999; -. DR SASBDB; Q03164; -. DR SMR; Q03164; -. DR BioGRID; 110443; 322. DR ComplexPortal; CPX-5850; Histone-lysine N-methyltransferase complex, KMT2A variant. DR CORUM; Q03164; -. DR DIP; DIP-29221N; -. DR ELM; Q03164; -. DR FunCoup; Q03164; 3961. DR IntAct; Q03164; 132. DR MINT; Q03164; -. DR NDEx; IQUERY-CP-KMT2A; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000436786; -. DR BindingDB; Q03164; -. DR ChEMBL; CHEMBL1293299; -. DR CarbonylDB; Q03164; -. DR GlyConnect; Q03164; 1 N-Linked glycan (1 site). DR GlyCosmos; Q03164; 17 sites, 4 glycans. DR GlyGen; Q03164; 47 sites, 4 N-linked glycans (3 sites), 2 O-linked glycans (35 sites). DR iPTMnet; Q03164; -. DR PhosphoSitePlus; Q03164; -. DR SwissPalm; Q03164; -. DR BioMuta; KMT2A; -. DR DMDM; 146345435; -. DR jPOST; Q03164; -. DR MassIVE; Q03164; -. DR PaxDb; 9606-ENSP00000436786; -. DR PeptideAtlas; Q03164; -. DR ProteomicsDB; 23014; -. DR ProteomicsDB; 58195; -. [Q03164-1] DR ProteomicsDB; 58196; -. [Q03164-2] DR Pumba; Q03164; -. DR Antibodypedia; 18629; 487 antibodies from 38 providers. DR DNASU; 4297; -. DR Ensembl; ENST00000389506.10; ENSP00000374157.5; ENSG00000118058.26. [Q03164-1] DR Ensembl; ENST00000534358.8; ENSP00000436786.2; ENSG00000118058.26. [Q03164-3] DR Ensembl; ENST00000649699.1; ENSP00000496927.1; ENSG00000118058.26. [Q03164-2] DR GeneID; 4297; -. DR KEGG; hsa:4297; -. DR MANE-Select; ENST00000534358.8; ENSP00000436786.2; NM_001197104.2; NP_001184033.1. [Q03164-3] DR UCSC; uc001pta.4; human. [Q03164-1] DR AGR; HGNC:7132; -. DR CIViC; 4297; 1 clinical assertion and 9 evidence items across 8 molecular profiles. DR ClinPGx; PA241; -. DR CTD; 4297; -. DR DisGeNET; 4297; -. DR GeneCards; KMT2A; -. DR GeneReviews; KMT2A; -. DR HGNC; HGNC:7132; KMT2A. DR HPA; ENSG00000118058; Low tissue specificity. DR MalaCards; KMT2A; -. DR MIM; 159555; gene+phenotype. DR MIM; 605130; phenotype. DR OpenTargets; ENSG00000118058; -. DR Orphanet; 98831; Acute myeloid leukemia with 11q23 abnormalities. DR Orphanet; 402017; Acute myeloid leukemia with t(9;11)(p22;q23). DR Orphanet; 98835; Acute undifferentiated leukemia. DR Orphanet; 585918; B-lymphoblastic leukemia/lymphoma with t(v;11q23.3). DR Orphanet; 589534; Mixed phenotype acute leukemia with t(9;22)(q34.1;q11.2). DR Orphanet; 589595; Mixed phenotype acute leukemia with t(v;11q23.3). DR Orphanet; 319182; Wiedemann-Steiner syndrome. DR VEuPathDB; HostDB:ENSG00000118058; -. DR eggNOG; KOG1084; Eukaryota. DR GeneTree; ENSGT00940000160099; -. DR HOGENOM; CLU_000208_2_0_1; -. DR InParanoid; Q03164; -. DR OMA; VVRSQQW; -. DR OrthoDB; 308383at2759; -. DR PAN-GO; Q03164; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q03164; -. DR BioCyc; MetaCyc:HS04188-MONOMER; -. DR PathwayCommons; Q03164; -. DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines. DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function. DR Reactome; R-HSA-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs. DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis. DR Reactome; R-HSA-9772755; Formation of WDR5-containing histone-modifying complexes. DR Reactome; R-HSA-9909649; Regulation of PD-L1(CD274) transcription. DR Reactome; R-HSA-9931510; Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes. DR Reactome; R-HSA-9931512; Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters. DR Reactome; R-HSA-9931521; The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex. DR Reactome; R-HSA-9976102; Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells). DR SignaLink; Q03164; -. DR SIGNOR; Q03164; -. DR Agora; ENSG00000118058; -. DR BioGRID-ORCS; 4297; 127 hits in 1158 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR ChiTaRS; KMT2A; human. DR EvolutionaryTrace; Q03164; -. DR GeneWiki; MLL_(gene); -. DR GenomeRNAi; 4297; -. DR Pharos; Q03164; Tchem. DR PRO; PR:Q03164; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q03164; protein. DR Bgee; ENSG00000118058; Expressed in ventricular zone and 215 other cell types or tissues. DR ExpressionAtlas; Q03164; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0035097; C:histone methyltransferase complex; IDA:UniProtKB. DR GO; GO:0071339; C:MLL1 complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0042800; F:histone H3K4 methyltransferase activity; IDA:UniProtKB. DR GO; GO:0140945; F:histone H3K4 monomethyltransferase activity; EXP:UniProtKB. DR GO; GO:0140999; F:histone H3K4 trimethyltransferase activity; IDA:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0003680; F:minor groove of adenine-thymine-rich DNA binding; NAS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0106363; F:protein-cysteine methyltransferase activity; IDA:UniProtKB. DR GO; GO:0045322; F:unmethylated CpG binding; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl. DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB. DR GO; GO:0060216; P:definitive hemopoiesis; IEA:Ensembl. DR GO; GO:0035162; P:embryonic hemopoiesis; TAS:UniProtKB. DR GO; GO:0051899; P:membrane depolarization; IEA:Ensembl. DR GO; GO:0090310; P:negative regulation of DNA methylation-dependent heterochromatin formation; IMP:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB. DR GO; GO:0035864; P:response to potassium ion; IEA:Ensembl. DR GO; GO:0045064; P:T-helper 2 cell differentiation; IDA:UniProtKB. DR GO; GO:0045815; P:transcription initiation-coupled chromatin remodeling; IDA:UniProtKB. DR CDD; cd05493; Bromo_ALL-1; 1. DR CDD; cd15693; ePHD_KMT2A; 1. DR CDD; cd15588; PHD1_KMT2A; 1. DR CDD; cd15590; PHD2_KMT2A; 1. DR CDD; cd15592; PHD3_KMT2A; 1. DR CDD; cd19170; SET_KMT2A_2B; 1. DR DisProt; DP01116; -. DR FunFam; 3.30.160.360:FF:000002; Histone-lysine N-methyltransferase; 1. DR FunFam; 3.30.160.360:FF:000003; Histone-lysine N-methyltransferase; 1. DR FunFam; 3.30.40.10:FF:000002; Histone-lysine N-methyltransferase; 1. DR FunFam; 3.30.40.10:FF:000071; Histone-lysine N-methyltransferase; 1. DR FunFam; 3.30.40.10:FF:000089; Histone-lysine N-methyltransferase; 1. DR FunFam; 2.170.270.10:FF:000149; Myeloid/lymphoid or mixed-lineage leukemia; 1. DR Gene3D; 3.30.160.360; -; 2. DR Gene3D; 6.10.250.2390; -; 1. DR Gene3D; 1.20.920.10; Bromodomain-like; 1. DR Gene3D; 2.170.270.10; SET domain; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 3. DR IDEAL; IID00379; -. DR InterPro; IPR001487; Bromodomain. DR InterPro; IPR036427; Bromodomain-like_sf. DR InterPro; IPR034732; EPHD. DR InterPro; IPR003889; FYrich_C. DR InterPro; IPR003888; FYrich_N. DR InterPro; IPR047219; KMT2A_2B_SET. DR InterPro; IPR041958; KMT2A_ePHD. DR InterPro; IPR042023; KMT2A_PHD1. DR InterPro; IPR042025; KMT2A_PHD2. DR InterPro; IPR044133; KMT2A_PHD3. DR InterPro; IPR016569; MeTrfase_trithorax. DR InterPro; IPR003616; Post-SET_dom. DR InterPro; IPR001214; SET_dom. DR InterPro; IPR046341; SET_dom_sf. DR InterPro; IPR002857; Znf_CXXC. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR001965; Znf_PHD. DR InterPro; IPR019787; Znf_PHD-finger. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR45838:SF2; HISTONE-LYSINE N-METHYLTRANSFERASE 2A; 1. DR PANTHER; PTHR45838; HISTONE-LYSINE-N-METHYLTRANSFERASE 2 KMT2 FAMILY MEMBER; 1. DR Pfam; PF05965; FYRC; 1. DR Pfam; PF05964; FYRN; 1. DR Pfam; PF00628; PHD; 2. DR Pfam; PF00856; SET; 1. DR Pfam; PF02008; zf-CXXC; 1. DR Pfam; PF13771; zf-HC5HC2H; 1. DR PIRSF; PIRSF010354; Methyltransferase_trithorax; 1. DR SMART; SM00297; BROMO; 1. DR SMART; SM00542; FYRC; 1. DR SMART; SM00541; FYRN; 1. DR SMART; SM00249; PHD; 4. DR SMART; SM00508; PostSET; 1. DR SMART; SM00317; SET; 1. DR SUPFAM; SSF47370; Bromodomain; 1. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 2. DR SUPFAM; SSF82199; SET domain; 1. DR PROSITE; PS50014; BROMODOMAIN_2; 1. DR PROSITE; PS51805; EPHD; 1. DR PROSITE; PS51543; FYRC; 1. DR PROSITE; PS51542; FYRN; 1. DR PROSITE; PS50868; POST_SET; 1. DR PROSITE; PS50280; SET; 1. DR PROSITE; PS51058; ZF_CXXC; 1. DR PROSITE; PS01359; ZF_PHD_1; 3. DR PROSITE; PS50016; ZF_PHD_2; 3. DR PDBsum; 2AGH; -. DR PDBsum; 2J2S; -. DR PDBsum; 2JYI; -. DR PDBsum; 2KKF; -. DR PDBsum; 2KU7; -. DR PDBsum; 2KYU; -. DR PDBsum; 2LXS; -. DR PDBsum; 2LXT; -. DR PDBsum; 2MSR; -. DR PDBsum; 2MTN; -. DR PDBsum; 2W5Y; -. DR PDBsum; 2W5Z; -. DR PDBsum; 3EG6; -. DR PDBsum; 3EMH; -. DR PDBsum; 3LQH; -. DR PDBsum; 3LQI; -. DR PDBsum; 3LQJ; -. DR PDBsum; 3P4F; -. DR PDBsum; 3U85; -. DR PDBsum; 3U88; -. DR PDBsum; 4ESG; -. DR PDBsum; 4GQ6; -. DR PDBsum; 4NW3; -. DR PDBsum; 5F5E; -. DR PDBsum; 5F6L; -. DR PDBsum; 5SVH; -. DR PDBsum; 6EMQ; -. DR PDBsum; 6KIU; -. DR PDBsum; 6KIV; -. DR PDBsum; 6KIX; -. DR PDBsum; 6KIZ; -. DR PDBsum; 6PWV; -. DR PDBsum; 6PWW; -. DR PDBsum; 6U9K; -. DR PDBsum; 6U9M; -. DR PDBsum; 6U9N; -. DR PDBsum; 6U9R; -. DR PDBsum; 6W5I; -. DR PDBsum; 6W5M; -. DR PDBsum; 6W5N; -. DR PDBsum; 7MBM; -. DR PDBsum; 7MBN; -. DR PDBsum; 7RZD; -. DR PDBsum; 7RZJ; -. DR PDBsum; 7S79; -. DR PDBsum; 7S7D; -. DR PDBsum; 7S8A; -. DR PDBsum; 7S8E; -. DR PDBsum; 7S8F; -. DR PDBsum; 7U5V; -. DR PDBsum; 7W67; -. DR PDBsum; 7W6A; -. DR PDBsum; 7W6I; -. DR PDBsum; 7W6J; -. DR PDBsum; 7ZEY; -. DR PDBsum; 7ZEZ; -. DR PDBsum; 9C4S; -. DR PDBsum; 9C4T; -. DR PDBsum; 9C4U; -. DR PDBsum; 9C4V; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; KW Biological rhythms; Bromodomain; Chromatin regulator; KW Chromosomal rearrangement; Direct protein sequencing; DNA-binding; KW Host-virus interaction; Isopeptide bond; Metal-binding; Methylation; KW Methyltransferase; Nucleus; Phosphoprotein; Proteomics identification; KW Proto-oncogene; Reference proteome; Repeat; S-adenosyl-L-methionine; KW Transcription; Transcription regulation; Transferase; Ubl conjugation; KW Zinc; Zinc-finger. FT CHAIN 1..3969 FT /note="Histone-lysine N-methyltransferase 2A" FT /id="PRO_0000124876" FT CHAIN 1..2718 FT /note="MLL cleavage product N320" FT /evidence="ECO:0000305|PubMed:12482972, FT ECO:0000305|PubMed:14636557" FT /id="PRO_0000390949" FT CHAIN 2719..3969 FT /note="MLL cleavage product C180" FT /evidence="ECO:0000305|PubMed:12482972, FT ECO:0000305|PubMed:14636557" FT /id="PRO_0000390950" FT DOMAIN 1635..1765 FT /note="Bromo" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035" FT DOMAIN 2018..2074 FT /note="FYR N-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00875" FT DOMAIN 3666..3747 FT /note="FYR C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00876" FT DOMAIN 3829..3945 FT /note="SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT DOMAIN 3953..3969 FT /note="Post-SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155" FT DNA_BIND 169..180 FT /note="A.T hook 1" FT DNA_BIND 217..227 FT /note="A.T hook 2" FT DNA_BIND 301..309 FT /note="A.T hook 3" FT ZN_FING 1147..1195 FT /note="CXXC-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034" FT ZN_FING 1431..1482 FT /note="PHD-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1479..1533 FT /note="PHD-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1566..1627 FT /note="PHD-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1870..1910 FT /note="C2HC pre-PHD-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146" FT ZN_FING 1931..1978 FT /note="PHD-type 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146" FT REGION 1..108 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 132..253 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 301..352 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 445..585 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 713..780 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 798..949 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1038..1066 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1106..1166 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1200..1375 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1584..1600 FT /note="Interaction with histone H3K4me3" FT /evidence="ECO:0000269|PubMed:20677832" FT REGION 1663..1713 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1806..1869 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2081..2133 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2145..2232 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2275..2333 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2373..2460 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2475..2618 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2647..2675 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2713..2821 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2961..3064 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3166..3244 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3464..3608 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3620..3643 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3785..3808 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 6..25 FT /note="Menin-binding motif (MBM)" FT /evidence="ECO:0000269|PubMed:22327296" FT MOTIF 123..134 FT /note="Integrase domain-binding motif 1 (IBM1)" FT /evidence="ECO:0000269|PubMed:25305204" FT MOTIF 147..152 FT /note="Integrase domain-binding motif 2 (IBM2)" FT /evidence="ECO:0000269|PubMed:25305204" FT MOTIF 2847..2855 FT /note="9aaTAD" FT /evidence="ECO:0000269|PubMed:17467953" FT MOTIF 3762..3767 FT /note="WDR5 interaction motif (WIN)" FT /evidence="ECO:0000269|PubMed:18829459, FT ECO:0000269|PubMed:22665483" FT COMPBIAS 15..29 FT /note="Gly residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 59..69 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 77..104 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 202..220 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 237..253 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 323..347 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 452..491 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 546..559 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 560..573 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 716..732 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 762..780 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 798..808 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 820..841 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 846..890 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1043..1062 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1220..1232 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1233..1243 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1248..1273 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1284..1300 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1304..1313 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1826..1847 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2095..2115 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2214..2232 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2283..2302 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2310..2319 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2406..2421 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2432..2442 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2543..2563 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2573..2592 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2726..2741 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2744..2782 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2784..2795 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2796..2805 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2812..2821 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2963..2972 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3016..3030 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3039..3064 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3171..3182 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3198..3216 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3218..3233 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3476..3489 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3508..3529 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3591..3603 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 1155 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1158 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1161 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1167 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1170 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1173 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1189 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 1194 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509, FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4NW3" FT BINDING 3839 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190, FT ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:26886794, FT ECO:0007744|PDB:2W5Y, ECO:0007744|PDB:5F5E, FT ECO:0007744|PDB:5F6L" FT BINDING 3841 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190, FT ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:26886794, FT ECO:0007744|PDB:2W5Y, ECO:0007744|PDB:5F5E, FT ECO:0007744|PDB:5F6L" FT BINDING 3883 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190, FT ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:26886794, FT ECO:0007744|PDB:2W5Z, ECO:0007744|PDB:5F5E" FT BINDING 3906..3907 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:19187761, FT ECO:0000269|PubMed:26886794, ECO:0007744|PDB:2W5Y, FT ECO:0007744|PDB:5F5E, ECO:0007744|PDB:5F6L" FT BINDING 3909 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:19187761, ECO:0007744|PDB:2W5Y, FT ECO:0007744|PDB:2W5Z, ECO:0007744|PDB:5F5E, FT ECO:0007744|PDB:5F6L" FT BINDING 3957 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:19187761, ECO:0007744|PDB:2W5Y, FT ECO:0007744|PDB:2W5Z, ECO:0007744|PDB:5F5E, FT ECO:0007744|PDB:5F6L" FT BINDING 3958 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190, FT ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:26886794, FT ECO:0007744|PDB:2W5Y, ECO:0007744|PDB:5F5E, FT ECO:0007744|PDB:5F6L" FT BINDING 3959 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:19187761, ECO:0007744|PDB:2W5Y, FT ECO:0007744|PDB:2W5Z, ECO:0007744|PDB:5F5E, FT ECO:0007744|PDB:5F6L" FT BINDING 3964 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:19187761, ECO:0007744|PDB:2W5Y, FT ECO:0007744|PDB:2W5Z, ECO:0007744|PDB:5F6L" FT SITE 1334..1335 FT /note="Breakpoint for translocation to form KMT2A-ZFYVE19 FT oncogene" FT SITE 1362..1363 FT /note="Breakpoint for translocation to form KMT2A-AF3P21 FT and KMT2A-KNL1 oncogenes" FT SITE 1362..1363 FT /note="Breakpoint for translocation to form KMT2A-CENPK FT oncogene" FT SITE 1362 FT /note="Breakpoint for translocation to form KMT2A-FRYL FT fusion protein" FT SITE 1406..1407 FT /note="Breakpoint for translocation to form KMT2A-AFF4 FT fusion protein" FT SITE 1444..1445 FT /note="Breakpoint for translocation to form KMT2A-GAS7 FT oncogene" FT SITE 1444..1445 FT /note="Breakpoint for translocation to form KMT2A-LPP" FT SITE 2666..2667 FT /note="Cleavage; by TASP1, site 1" FT /evidence="ECO:0000269|PubMed:14636557" FT SITE 2718..2719 FT /note="Cleavage; by TASP1, site 2" FT /evidence="ECO:0000269|PubMed:14636557" FT SITE 3765 FT /note="Important for WDR5-recognition and binding" FT /evidence="ECO:0000269|PubMed:19556245" FT MOD_RES 136 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:29997176" FT MOD_RES 142 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:29997176" FT MOD_RES 153 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:29997176, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231" FT MOD_RES 197 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 239 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P55200" FT MOD_RES 373 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P55200" FT MOD_RES 518 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 636 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 680 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 840 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 926 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1056 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1130 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 1235 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 1837 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1845 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1858 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:23186163" FT MOD_RES 2098 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 2147 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 2151 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 2201 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 2525 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 2611 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2796 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2955 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 2958 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P55200" FT MOD_RES 3036 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 3372 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 3462 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P55200" FT MOD_RES 3511 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 3515 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 3527 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 3882 FT /note="S-methylcysteine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:24235145" FT CROSSLNK 2528 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1407..1444 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:7598802" FT /id="VSP_006666" FT VAR_SEQ 1603 FT /note="S -> SGTE (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10706619, FT ECO:0000303|PubMed:1423625" FT /id="VSP_046879" FT VARIANT 30 FT /note="A -> G (in dbSNP:rs9332745)" FT /evidence="ECO:0000269|PubMed:8703835" FT /id="VAR_021317" FT VARIANT 53 FT /note="A -> V (in dbSNP:rs9332747)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021318" FT VARIANT 502 FT /note="E -> K (in dbSNP:rs9332772)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021319" FT VARIANT 1975 FT /note="Q -> P (in dbSNP:rs693598)" FT /id="VAR_052652" FT VARIANT 2319 FT /note="S -> T (in dbSNP:rs9332837)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021320" FT VARIANT 2354 FT /note="P -> R (in dbSNP:rs9332838)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021321" FT VARIANT 2387 FT /note="Q -> R (in dbSNP:rs9332839)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021322" FT VARIANT 3714 FT /note="V -> I (in dbSNP:rs9332859)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021323" FT VARIANT 3773 FT /note="S -> A (in dbSNP:rs9332861)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021324" FT MUTAGEN 6 FT /note="R->A: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 7 FT /note="W->A: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 8 FT /note="R->A: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 9 FT /note="F->A: Loss of interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 9 FT /note="F->H,Y: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 10 FT /note="P->A: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 11 FT /note="A->R: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 12 FT /note="R->A: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 13 FT /note="P->A: Reduced interaction with MEN1." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 24 FT /note="R->E: Reduced interaction with MEN1; when associated FT with E-25." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 25 FT /note="R->E: Reduced interaction with MEN1; when associated FT with E-24." FT /evidence="ECO:0000269|PubMed:22327296" FT MUTAGEN 129 FT /note="F->A: Weakly affects interaction with PSIP1 whereas FT significantly decreases interaction of KMT2A-MEN1 complex FT with PSIP1. Reduced interaction with PSIP1; when associated FT with A-133." FT /evidence="ECO:0000269|PubMed:25082813, FT ECO:0000269|PubMed:25305204" FT MUTAGEN 132 FT /note="V->A: Reduced interaction with PSIP1; when FT associated with A-133." FT /evidence="ECO:0000269|PubMed:29997176" FT MUTAGEN 133 FT /note="F->A: Reduced interaction with PSIP1; when FT associated with A-129 or A-132." FT /evidence="ECO:0000269|PubMed:25082813, FT ECO:0000269|PubMed:29997176" FT MUTAGEN 136 FT /note="S->D: Phosphomimetic mutant. Significant increase in FT interaction with PSIP1; when associated with D-142." FT /evidence="ECO:0000269|PubMed:29997176" FT MUTAGEN 142 FT /note="S->D: Phosphomimetic mutant. Significant increase in FT interaction with PSIP1; when associated with D-136." FT /evidence="ECO:0000269|PubMed:29997176" FT MUTAGEN 144 FT /note="E->Q: Loss of interaction with PSIP1; when FT associated with Q-146 and A-148." FT /evidence="ECO:0000269|PubMed:25082813" FT MUTAGEN 146 FT /note="E->Q: Loss of interaction with PSIP1; when FT associated with Q-144 and A-148." FT /evidence="ECO:0000269|PubMed:25082813" FT MUTAGEN 148 FT /note="F->A: Reduced interaction with PSIP1. Loss of FT interaction with PSIP1; when associated with A-149 or Q-144 FT and Q-146." FT /evidence="ECO:0000269|PubMed:25082813, FT ECO:0000269|PubMed:25305204" FT MUTAGEN 149 FT /note="L->A: Loss of interaction with PSIP1; when FT associated with A-148." FT /evidence="ECO:0000269|PubMed:25305204" FT MUTAGEN 151 FT /note="F->A: Reduced interaction with PSIP1." FT /evidence="ECO:0000269|PubMed:25082813" FT MUTAGEN 1150 FT /note="R->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:20010842" FT MUTAGEN 1151 FT /note="R->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1153 FT /note="R->A: No effect on stability or DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1154 FT /note="R->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:20010842" FT MUTAGEN 1155 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1158 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1161 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1162 FT /note="Q->A: No effect on stability or DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1166 FT /note="D->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1167 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1170 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1172 FT /note="N->A: No effect on stability or DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1173 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1175 FT /note="D->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1176 FT /note="K->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1178..1181 FT /note="KFGG->AAAA: Abolishes zinc-binding and stability of FT the CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1178 FT /note="K->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1179 FT /note="F->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1183 FT /note="N->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1185 FT /note="K->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:20010842" FT MUTAGEN 1186 FT /note="K->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1187 FT /note="Q->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:20010842" FT MUTAGEN 1188 FT /note="C->A: No effect on stability or DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:20010842" FT MUTAGEN 1188 FT /note="C->D: Abolishes DNA-binding and increases CpG FT methylation of the HOXA9 promoter region. Does not lead to FT the development of leukemia when overexpressed in mice as FT gene fusion with MLLT3." FT /evidence="ECO:0000269|PubMed:20010842" FT MUTAGEN 1189 FT /note="C->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1192 FT /note="R->A: Abolishes zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1193 FT /note="K->A: Impairs DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798, FT ECO:0000269|PubMed:20010842" FT MUTAGEN 1194 FT /note="C->A: Impairs zinc-binding and stability of the FT CXXC-type zinc finger and causes loss of DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1195 FT /note="Q->A: No effect on stability or DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1196 FT /note="N->A: No effect on stability or DNA-binding." FT /evidence="ECO:0000269|PubMed:16990798" FT MUTAGEN 1197 FT /note="L->A: Mildly decreases DNA-binding." FT /evidence="ECO:0000269|PubMed:20010842" FT MUTAGEN 1200 FT /note="M->A: No effect on DNA-binding." FT /evidence="ECO:0000269|PubMed:20010842" FT MUTAGEN 1581 FT /note="Y->A: Decreases affinity for histone H3K4me3." FT /evidence="ECO:0000269|PubMed:20541251" FT MUTAGEN 1587 FT /note="Q->A: Decreases affinity for histone H3K4me3." FT /evidence="ECO:0000269|PubMed:20541251" FT MUTAGEN 1594 FT /note="W->A: Abolishes interaction with histone H3K4me3." FT /evidence="ECO:0000269|PubMed:20677832" FT MUTAGEN 1594 FT /note="W->E: Decreases affinity for histone H3K4me3." FT /evidence="ECO:0000269|PubMed:20541251" FT MUTAGEN 1617 FT /note="V->A: Decreases binding affinity for PPIE." FT /evidence="ECO:0000269|PubMed:20677832" FT MUTAGEN 1619 FT /note="Y->A: May perturb protein folding and thereby FT decrease binding affinity for PPIE." FT /evidence="ECO:0000269|PubMed:20677832" FT MUTAGEN 2666..2667 FT /note="DG->AA: Reduces cleavage without abolishing it. FT Abolishes cleavage by TASP1; when associated with FT 2718-A--A-2720." FT /evidence="ECO:0000269|PubMed:14636557" FT MUTAGEN 2718..2720 FT /note="DGV->AAA: Abolishes cleavage by TASP1; when FT associated with 2666-A-A-2667." FT /evidence="ECO:0000269|PubMed:12482972, FT ECO:0000269|PubMed:14636557" FT MUTAGEN 3763 FT /note="S->A: Increased interaction with WDR5." FT /evidence="ECO:0000269|PubMed:22665483" FT MUTAGEN 3765 FT /note="R->A: Loss of interaction with the WRAD complex and FT WDR5." FT /evidence="ECO:0000269|PubMed:18840606, FT ECO:0000269|PubMed:22665483" FT MUTAGEN 3769 FT /note="H->A,F: Slight decrease in interaction with WDR5." FT /evidence="ECO:0000269|PubMed:18840606" FT MUTAGEN 3769 FT /note="H->Y: Increased interaction with WDR5." FT /evidence="ECO:0000269|PubMed:22665483" FT MUTAGEN 3858 FT /note="Y->A: Impairs methyltransferase activity toward FT unmodified or monomethylated H3K4me." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3858 FT /note="Y->F: Slightly affects methyltransferase activity FT toward unmodified or monomethylated H3K4me." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3861 FT /note="N->I: Leads to stable interaction with ASH2L and FT RBBP5 in the absence of WDR5; when associated with L-3867." FT /evidence="ECO:0000269|PubMed:26886794" FT MUTAGEN 3861 FT /note="N->T: Leads to stable interaction with ASH2L and FT RBBP5 in the absence of WDR5; when associated with V-3867." FT /evidence="ECO:0000269|PubMed:26886794" FT MUTAGEN 3864 FT /note="R->A: Disrupts interaction with ASH2L and RBBP5 and FT nearly abolishes histone methyltransferase activity." FT /evidence="ECO:0000269|PubMed:26886794" FT MUTAGEN 3867 FT /note="Q->A: Slightly affects methyltransferase activity of FT the enzyme alone, while it impairs methyltransferase FT activity in complex; when associated with A-3871." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3867 FT /note="Q->L: Leads to stable interaction with ASH2L and FT RBBP5 in the absence of WDR5; when associated with I-3861." FT /evidence="ECO:0000269|PubMed:26886794" FT MUTAGEN 3867 FT /note="Q->V: Leads to stable interaction with ASH2L and FT RBBP5 in the absence of WDR5; when associated with T-3861." FT /evidence="ECO:0000269|PubMed:26886794" FT MUTAGEN 3869 FT /note="D->A: Does not affect methyltransferase activity of FT the enzyme alone or in complex; when associated with FT A-3872." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3871 FT /note="R->A: Slightly affects methyltransferase activity of FT the enzyme alone, while it impairs methyltransferase FT activity in complex; when associated with A-3867." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3872 FT /note="E->A: Does not affect methyltransferase activity of FT the enzyme alone or in complex; when associated with FT A-3869." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3874 FT /note="Y->A: Affects methyltransferase activity of the FT enzyme alone, while it does not affect methyltransferase FT activity in complex; when associated with A-3878." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3878 FT /note="K->A: Affects methyltransferase activity of the FT enzyme alone, while it does not affect methyltransferase FT activity in complex; when associated with A-3874." FT /evidence="ECO:0000269|PubMed:19187761" FT MUTAGEN 3882 FT /note="C->A,S: Abolished auto-methylation." FT /evidence="ECO:0000269|PubMed:24235145" FT MUTAGEN 3906 FT /note="N->A: Loss of the histone H3 methyltransferase FT activity. Abolishes interaction with FT S-adenosyl-L-methionine." FT /evidence="ECO:0000269|PubMed:19556245, FT ECO:0000269|PubMed:25561738" FT MUTAGEN 3942 FT /note="Y->A,F: Impairs methyltransferase activity toward FT unmodified or monomethylated H3K4me." FT /evidence="ECO:0000269|PubMed:19187761, FT ECO:0000269|PubMed:19556245" FT MUTAGEN 3942 FT /note="Y->F: Shifts from a specific monomethyltransferase FT to a di- and trimethyltransferase activity." FT /evidence="ECO:0000269|PubMed:19187761, FT ECO:0000269|PubMed:19556245" FT CONFLICT 144 FT /note="E -> ELTTQIPCSWRTKGHIHDKKTEPFRLLAWSWCLN (in Ref. 2; FT CAA93625)" FT /evidence="ECO:0000305" FT CONFLICT 556 FT /note="Q -> E (in Ref. 2; CAA93625 and 6; L04731)" FT /evidence="ECO:0000305" FT CONFLICT 1347 FT /note="V -> A (in Ref. 13; AAG26335)" FT /evidence="ECO:0000305" FT CONFLICT 1487 FT /note="R -> G (in Ref. 12; AAA18644)" FT /evidence="ECO:0000305" FT CONFLICT 1490 FT /note="Q -> R (in Ref. 13; AAG26335)" FT /evidence="ECO:0000305" FT CONFLICT 1507 FT /note="P -> L (in Ref. 13; AAG26335)" FT /evidence="ECO:0000305" FT CONFLICT 1513 FT /note="N -> T (in Ref. 13; AAG26335)" FT /evidence="ECO:0000305" FT CONFLICT 1600 FT /note="E -> G (in Ref. 13; AAG26335)" FT /evidence="ECO:0000305" FT CONFLICT 1616 FT /note="S -> C (in Ref. 11; AAB34770)" FT /evidence="ECO:0000305" FT CONFLICT 1937 FT /note="Q -> H (in Ref. 8; AAA92511)" FT /evidence="ECO:0000305" FT CONFLICT 2181 FT /note="P -> S (in Ref. 8; AAA92511)" FT /evidence="ECO:0000305" FT CONFLICT 3556 FT /note="K -> N (in Ref. 6; L04731)" FT /evidence="ECO:0000305" FT CONFLICT 3718 FT /note="R -> G (in Ref. 2; CAA93625)" FT /evidence="ECO:0000305" FT CONFLICT 3759 FT /note="N -> D (in Ref. 2; CAA93625)" FT /evidence="ECO:0000305" FT CONFLICT 3813 FT /note="D -> G (in Ref. 2; CAA93625)" FT /evidence="ECO:0000305" FT CONFLICT 3901 FT /note="A -> R (in Ref. 1; AAA58669)" FT /evidence="ECO:0000305" FT HELIX 114..133 FT /evidence="ECO:0007829|PDB:3U88" FT STRAND 135..138 FT /evidence="ECO:0007829|PDB:2MTN" FT STRAND 140..145 FT /evidence="ECO:0007829|PDB:6EMQ" FT STRAND 150..152 FT /evidence="ECO:0007829|PDB:2MSR" FT HELIX 748..754 FT /evidence="ECO:0007829|PDB:7S79" FT STRAND 1151..1154 FT /evidence="ECO:0007829|PDB:2J2S" FT STRAND 1156..1158 FT /evidence="ECO:0007829|PDB:4NW3" FT HELIX 1159..1162 FT /evidence="ECO:0007829|PDB:4NW3" FT STRAND 1168..1170 FT /evidence="ECO:0007829|PDB:4NW3" FT HELIX 1171..1175 FT /evidence="ECO:0007829|PDB:4NW3" FT HELIX 1177..1179 FT /evidence="ECO:0007829|PDB:4NW3" FT STRAND 1183..1185 FT /evidence="ECO:0007829|PDB:2J2S" FT HELIX 1187..1189 FT /evidence="ECO:0007829|PDB:2J2S" FT TURN 1190..1192 FT /evidence="ECO:0007829|PDB:4NW3" FT STRAND 1197..1200 FT /evidence="ECO:0007829|PDB:2J2S" FT TURN 1204..1206 FT /evidence="ECO:0007829|PDB:2J2S" FT STRAND 1566..1568 FT /evidence="ECO:0007829|PDB:3LQI" FT TURN 1570..1572 FT /evidence="ECO:0007829|PDB:3LQH" FT STRAND 1575..1577 FT /evidence="ECO:0007829|PDB:3LQI" FT TURN 1578..1582 FT /evidence="ECO:0007829|PDB:2KYU" FT STRAND 1585..1587 FT /evidence="ECO:0007829|PDB:3LQH" FT TURN 1589..1591 FT /evidence="ECO:0007829|PDB:3LQH" FT STRAND 1594..1596 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1597..1599 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1604..1612 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1614..1617 FT /evidence="ECO:0007829|PDB:3LQH" FT TURN 1622..1624 FT /evidence="ECO:0007829|PDB:3LQH" FT STRAND 1627..1629 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1631..1652 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1655..1661 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1708..1716 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1723..1740 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1745..1765 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 1771..1773 FT /evidence="ECO:0007829|PDB:3LQH" FT HELIX 2847..2855 FT /evidence="ECO:0007829|PDB:5SVH" FT HELIX 3764..3766 FT /evidence="ECO:0007829|PDB:4ESG" FT HELIX 3796..3799 FT /evidence="ECO:0007829|PDB:2W5Y" FT HELIX 3805..3808 FT /evidence="ECO:0007829|PDB:2W5Y" FT HELIX 3809..3811 FT /evidence="ECO:0007829|PDB:2W5Y" FT HELIX 3813..3815 FT /evidence="ECO:0007829|PDB:7W6A" FT HELIX 3816..3821 FT /evidence="ECO:0007829|PDB:5F5E" FT HELIX 3823..3830 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3831..3835 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3837..3847 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3854..3857 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3860..3864 FT /evidence="ECO:0007829|PDB:5F5E" FT HELIX 3865..3867 FT /evidence="ECO:0007829|PDB:5F5E" FT HELIX 3868..3878 FT /evidence="ECO:0007829|PDB:5F5E" FT HELIX 3880..3882 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3884..3886 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3888..3894 FT /evidence="ECO:0007829|PDB:5F5E" FT TURN 3896..3898 FT /evidence="ECO:0007829|PDB:5F5E" FT HELIX 3901..3904 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3912..3920 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3923..3932 FT /evidence="ECO:0007829|PDB:5F5E" FT STRAND 3939..3942 FT /evidence="ECO:0007829|PDB:5F5E" FT HELIX 3946..3948 FT /evidence="ECO:0007829|PDB:5F6L" FT HELIX 3951..3953 FT /evidence="ECO:0007829|PDB:7W67" SQ SEQUENCE 3969 AA; 431764 MW; 1150F37EAB1430D3 CRC64; MAHSCRWRFP ARPGTTGGGG GGGRRGLGGA PRQRVPALLL PPGPPVGGGG PGAPPSPPAV AAAAAAAGSS GAGVPGGAAA ASAASSSSAS SSSSSSSSAS SGPALLRVGP GFDAALQVSA AIGTNLRRFR AVFGESGGGG GSGEDEQFLG FGSDEEVRVR SPTRSPSVKT SPRKPRGRPR SGSDRNSAIL SDPSVFSPLN KSETKSGDKI KKKDSKSIEK KRGRPPTFPG VKIKITHGKD ISELPKGNKE DSLKKIKRTP SATFQQATKI KKLRAGKLSP LKSKFKTGKL QIGRKGVQIV RRRGRPPSTE RIKTPSGLLI NSELEKPQKV RKDKEGTPPL TKEDKTVVRQ SPRRIKPVRI IPSSKRTDAT IAKQLLQRAK KGAQKKIEKE AAQLQGRKVK TQVKNIRQFI MPVVSAISSR IIKTPRRFIE DEDYDPPIKI ARLESTPNSR FSAPSCGSSE KSSAASQHSS QMSSDSSRSS SPSVDTSTDS QASEEIQVLP EERSDTPEVH PPLPISQSPE NESNDRRSRR YSVSERSFGS RTTKKLSTLQ SAPQQQTSSS PPPPLLTPPP PLQPASSISD HTPWLMPPTI PLASPFLPAS TAPMQGKRKS ILREPTFRWT SLKHSRSEPQ YFSSAKYAKE GLIRKPIFDN FRPPPLTPED VGFASGFSAS GTAASARLFS PLHSGTRFDM HKRSPLLRAP RFTPSEAHSR IFESVTLPSN RTSAGTSSSG VSNRKRKRKV FSPIRSEPRS PSHSMRTRSG RLSSSELSPL TPPSSVSSSL SISVSPLATS ALNPTFTFPS HSLTQSGESA EKNQRPRKQT SAPAEPFSSS SPTPLFPWFT PGSQTERGRN KDKAPEELSK DRDADKSVEK DKSRERDRER EKENKRESRK EKRKKGSEIQ SSSALYPVGR VSKEKVVGED VATSSSAKKA TGRKKSSSHD SGTDITSVTL GDTTAVKTKI LIKKGRGNLE KTNLDLGPTA PSLEKEKTLC LSTPSSSTVK HSTSSIGSML AQADKLPMTD KRVASLLKKA KAQLCKIEKS KSLKQTDQPK AQGQESDSSE TSVRGPRIKH VCRRAAVALG RKRAVFPDDM PTLSALPWEE REKILSSMGN DDKSSIAGSE DAEPLAPPIK PIKPVTRNKA PQEPPVKKGR RSRRCGQCPG CQVPEDCGVC TNCLDKPKFG GRNIKKQCCK MRKCQNLQWM PSKAYLQKQA KAVKKKEKKS KTSEKKDSKE SSVVKNVVDS SQKPTPSARE DPAPKKSSSE PPPRKPVEEK SEEGNVSAPG PESKQATTPA SRKSSKQVSQ PALVIPPQPP TTGPPRKEVP KTTPSEPKKK QPPPPESGPE QSKQKKVAPR PSIPVKQKPK EKEKPPPVNK QENAGTLNIL STLSNGNSSK QKIPADGVHR IRVDFKEDCE AENVWEMGGL GILTSVPITP RVVCFLCASS GHVEFVYCQV CCEPFHKFCL EENERPLEDQ LENWCCRRCK FCHVCGRQHQ ATKQLLECNK CRNSYHPECL GPNYPTKPTK KKKVWICTKC VRCKSCGSTT PGKGWDAQWS HDFSLCHDCA KLFAKGNFCP LCDKCYDDDD YESKMMQCGK CDRWVHSKCE NLSDEMYEIL SNLPESVAYT CVNCTERHPA EWRLALEKEL QISLKQVLTA LLNSRTTSHL LRYRQAAKPP DLNPETEESI PSRSSPEGPD PPVLTEVSKQ DDQQPLDLEG VKRKMDQGNY TSVLEFSDDI VKIIQAAINS DGGQPEIKKA NSMVKSFFIR QMERVFPWFS VKKSRFWEPN KVSSNSGMLP NAVLPPSLDH NYAQWQEREE NSHTEQPPLM KKIIPAPKPK GPGEPDSPTP LHPPTPPILS TDRSREDSPE LNPPPGIEDN RQCALCLTYG DDSANDAGRL LYIGQNEWTH VNCALWSAEV FEDDDGSLKN VHMAVIRGKQ LRCEFCQKPG ATVGCCLTSC TSNYHFMCSR AKNCVFLDDK KVYCQRHRDL IKGEVVPENG FEVFRRVFVD FEGISLRRKF LNGLEPENIH MMIGSMTIDC LGILNDLSDC EDKLFPIGYQ CSRVYWSTTD ARKRCVYTCK IVECRPPVVE PDINSTVEHD ENRTIAHSPT SFTESSSKES QNTAEIISPP SPDRPPHSQT SGSCYYHVIS KVPRIRTPSY SPTQRSPGCR PLPSAGSPTP TTHEIVTVGD PLLSSGLRSI GSRRHSTSSL SPQRSKLRIM SPMRTGNTYS RNNVSSVSTT GTATDLESSA KVVDHVLGPL NSSTSLGQNT STSSNLQRTV VTVGNKNSHL DGSSSSEMKQ SSASDLVSKS SSLKGEKTKV LSSKSSEGSA HNVAYPGIPK LAPQVHNTTS RELNVSKIGS FAEPSSVSFS SKEALSFPHL HLRGQRNDRD QHTDSTQSAN SSPDEDTEVK TLKLSGMSNR SSIINEHMGS SSRDRRQKGK KSCKETFKEK HSSKSFLEPG QVTTGEEGNL KPEFMDEVLT PEYMGQRPCN NVSSDKIGDK GLSMPGVPKA PPMQVEGSAK ELQAPRKRTV KVTLTPLKME NESQSKNALK ESSPASPLQI ESTSPTEPIS ASENPGDGPV AQPSPNNTSC QDSQSNNYQN LPVQDRNLML PDGPKPQEDG SFKRRYPRRS ARARSNMFFG LTPLYGVRSY GEEDIPFYSS STGKKRGKRS AEGQVDGADD LSTSDEDDLY YYNFTRTVIS SGGEERLASH NLFREEEQCD LPKISQLDGV DDGTESDTSV TATTRKSSQI PKRNGKENGT ENLKIDRPED AGEKEHVTKS SVGHKNEPKM DNCHSVSRVK TQGQDSLEAQ LSSLESSRRV HTSTPSDKNL LDTYNTELLK SDSDNNNSDD CGNILPSDIM DFVLKNTPSM QALGESPESS SSELLNLGEG LGLDSNREKD MGLFEVFSQQ LPTTEPVDSS VSSSISAEEQ FELPLELPSD LSVLTTRSPT VPSQNPSRLA VISDSGEKRV TITEKSVASS ESDPALLSPG VDPTPEGHMT PDHFIQGHMD ADHISSPPCG SVEQGHGNNQ DLTRNSSTPG LQVPVSPTVP IQNQKYVPNS TDSPGPSQIS NAAVQTTPPH LKPATEKLIV VNQNMQPLYV LQTLPNGVTQ KIQLTSSVSS TPSVMETNTS VLGPMGGGLT LTTGLNPSLP TSQSLFPSAS KGLLPMSHHQ HLHSFPAATQ SSFPPNISNP PSGLLIGVQP PPDPQLLVSE SSQRTDLSTT VATPSSGLKK RPISRLQTRK NKKLAPSSTP SNIAPSDVVS NMTLINFTPS QLPNHPSLLD LGSLNTSSHR TVPNIIKRSK SSIMYFEPAP LLPQSVGGTA ATAAGTSTIS QDTSHLTSGS VSGLASSSSV LNVVSMQTTT TPTSSASVPG HVTLTNPRLL GTPDIGSISN LLIKASQQSL GIQDQPVALP PSSGMFPQLG TSQTPSTAAI TAASSICVLP STQTTGITAA SPSGEADEHY QLQHVNQLLA SKTGIHSSQR DLDSASGPQV SNFTQTVDAP NSMGLEQNKA LSSAVQASPT SPGGSPSSPS SGQRSASPSV PGPTKPKPKT KRFQLPLDKG NGKKHKVSHL RTSSSEAHIP DQETTSLTSG TGTPGAEAEQ QDTASVEQSS QKECGQPAGQ VAVLPEVQVT QNPANEQESA EPKTVEEEES NFSSPLMLWL QQEQKRKESI TEKKPKKGLV FEISSDDGFQ ICAESIEDAW KSLTDKVQEA RSNARLKQLS FAGVNGLRML GILHDAVVFL IEQLSGAKHC RNYKFRFHKP EEANEPPLNP HGSARAEVHL RKSAFDMFNF LASKHRQPPE YNPNDEEEEE VQLKSARRAT SMDLPMPMRF RHLKKTSKEA VGVYRSPIHG RGLFCKRNID AGEMVIEYAG NVIRSIQTDK REKYYDSKGI GCYMFRIDDS EVVDATMHGN AARFINHSCE PNCYSRVINI DGQKHIVIFA MRKIYRGEEL TYDYKFPIED ASNKLPCNCG AKKCRKFLN //