KMT2A_HUMAN
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 03-AUG-2022, entry version 250.
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;
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;
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;
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 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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 [53]
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 [54] {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 [55]
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 [56] {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 [57]
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 [58] {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 [59] {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 [60] {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 [61] {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 [62] {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 [63] {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 [64] {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 [65] {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 [66] {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 [67] {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 [68] {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 [69] {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 [70] {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 [71] {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:15960975, PubMed:12453419,
CC PubMed:15960975, PubMed:19556245, PubMed:19187761, PubMed:20677832,
CC PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL
CC complex, a multiprotein complex that mediates both methylation of 'Lys-
CC 4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of
CC histone H4 (H4K16ac) (PubMed:15960975, PubMed:12453419,
CC PubMed:15960975, PubMed:19556245, PubMed:24235145, PubMed:19187761,
CC PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalyzes methyl
CC group transfer from S-adenosyl-L-methionine to the epsilon-amino group
CC of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of
CC chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2
CC methylation marks at active chromatin sites where transcription and DNA
CC repair take place (PubMed:25561738, PubMed:15960975, PubMed:12453419,
CC PubMed:15960975, PubMed:19556245, PubMed:19187761, PubMed:20677832,
CC PubMed:21220120, PubMed:26886794). Has weak methyltransferase activity
CC by itself, and requires other component of the MLL1/MLL complex to
CC obtain full methyltransferase activity (PubMed:19187761,
CC PubMed:26886794). Has no activity toward histone H3 phosphorylated on
CC 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9',
CC while it has higher activity toward H3 acetylated on 'Lys-9'
CC (PubMed:19187761). Binds to unmethylated CpG elements in the promoter
CC of target genes and helps maintain them in the nonmethylated state
CC (PubMed:20010842). Required for transcriptional activation of HOXA9
CC (PubMed:12453419, PubMed:20677832, PubMed:20010842). Promotes PPP1R15A-
CC induced apoptosis (PubMed:10490642). Plays a critical role in the
CC control of circadian gene expression and is essential for the
CC transcriptional activation mediated by the CLOCK-ARNTL/BMAL1
CC heterodimer (By similarity). Establishes a permissive chromatin state
CC for circadian transcription by mediating a rhythmic methylation of
CC 'Lys-4' of histone H3 (H3K4me) and this histone modification directs
CC the circadian acetylation at H3K9 and H3K14 allowing the recruitment of
CC CLOCK-ARNTL/BMAL1 to chromatin (By similarity). Also has auto-
CC methylation activity on Cys-3882 in absence of histone H3 substrate
CC (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 = H(+) +
CC N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine;
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 = H(+) + N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60268, Rhea:RHEA-COMP:15540, Rhea:RHEA-
CC COMP:15543, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC 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 = H(+) + S-
CC adenosyl-L-homocysteine + S-methyl-L-cysteinyl-[protein];
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 N-
CC 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 BAP18, 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:19556245,
CC PubMed:23508102, PubMed:19187761, 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:19556245,
CC PubMed:18829459, PubMed:22665483, PubMed:18840606). 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:9537414,
CC PubMed:10490642). Interacts with ZNF335 (PubMed:23178126). Interacts
CC with CLOCK and ARNTL/BMAL1 in a circadian manner (By similarity).
CC Interacts with PPIE; this results in decreased histone H3
CC methyltransferase activity (PubMed:20677832, PubMed:20541251).
CC Interacts with CREBBP (PubMed:16253272). Interacts with the WRAD
CC complex composed of WDR5, RBBP5, ASH2L and DPY30 (PubMed:22665483).
CC Interacts (via MBM motif) with MEN1 (PubMed:22936661, PubMed:22327296,
CC PubMed:25305204). Interacts (via IBM motifs) with PSIP1 (via IBD
CC domain) with moderate affinity whereas the KMT2A-MEN1 complex interacts
CC with a greater affinity; MEN1 enhances interaction of KMT2A with PSIP1
CC (PubMed:22327296, PubMed:25305204, PubMed:25082813, 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 -!- 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=9; IntAct=EBI-591370, EBI-592823;
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=14; IntAct=EBI-591370, EBI-540834;
CC Q03164; Q9WTL8: Arntl; 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 -!- 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:20677832, PubMed:20541251). 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="http://atlasgeneticsoncology.org/Genes/MLLID13.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mll/";
CC ---------------------------------------------------------------------------
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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_001197104.1. [Q03164-3]
DR RefSeq; NP_005924.2; NM_005933.3. [Q03164-1]
DR PDB; 2AGH; NMR; -; C=2840-2869.
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; 7ZEY; NMR; -; B=1564-1627.
DR PDB; 7ZEZ; NMR; -; B=1564-1627.
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; 7ZEY; -.
DR PDBsum; 7ZEZ; -.
DR BMRB; Q03164; -.
DR SASBDB; Q03164; -.
DR SMR; Q03164; -.
DR BioGRID; 110443; 209.
DR ComplexPortal; CPX-5850; Histone-lysine N-methyltransferase complex, KMT2A variant.
DR CORUM; Q03164; -.
DR DIP; DIP-29221N; -.
DR ELM; Q03164; -.
DR IntAct; Q03164; 77.
DR MINT; Q03164; -.
DR STRING; 9606.ENSP00000436786; -.
DR BindingDB; Q03164; -.
DR ChEMBL; CHEMBL1293299; -.
DR CarbonylDB; Q03164; -.
DR GlyConnect; 2046; 1 N-Linked glycan (1 site).
DR GlyGen; Q03164; 17 sites, 2 N-linked glycans (1 site), 2 O-linked glycans (16 sites).
DR iPTMnet; Q03164; -.
DR PhosphoSitePlus; Q03164; -.
DR BioMuta; KMT2A; -.
DR DMDM; 146345435; -.
DR EPD; Q03164; -.
DR jPOST; Q03164; -.
DR MassIVE; Q03164; -.
DR MaxQB; Q03164; -.
DR PaxDb; Q03164; -.
DR PeptideAtlas; Q03164; -.
DR PRIDE; Q03164; -.
DR ProteomicsDB; 23014; -.
DR ProteomicsDB; 58195; -. [Q03164-1]
DR ProteomicsDB; 58196; -. [Q03164-2]
DR Antibodypedia; 18629; 476 antibodies from 36 providers.
DR DNASU; 4297; -.
DR Ensembl; ENST00000389506.10; ENSP00000374157.5; ENSG00000118058.24. [Q03164-1]
DR Ensembl; ENST00000534358.8; ENSP00000436786.2; ENSG00000118058.24. [Q03164-3]
DR Ensembl; ENST00000649699.1; ENSP00000496927.1; ENSG00000118058.24. [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 CTD; 4297; -.
DR DisGeNET; 4297; -.
DR GeneCards; 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 neXtProt; NX_Q03164; -.
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; 585877; B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality.
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 PharmGKB; PA241; -.
DR VEuPathDB; HostDB:ENSG00000118058; -.
DR eggNOG; KOG1084; Eukaryota.
DR GeneTree; ENSGT00940000160099; -.
DR HOGENOM; CLU_000208_2_0_1; -.
DR InParanoid; Q03164; -.
DR OMA; FPWFTSS; -.
DR OrthoDB; 738155at2759; -.
DR PhylomeDB; Q03164; -.
DR TreeFam; TF319820; -.
DR BioCyc; MetaCyc:HS04188-MON; -.
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 SignaLink; Q03164; -.
DR SIGNOR; Q03164; -.
DR BioGRID-ORCS; 4297; 121 hits in 1073 CRISPR screens.
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 213 other tissues.
DR ExpressionAtlas; Q03164; baseline and differential.
DR Genevisible; Q03164; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
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 methyltransferase activity (H3-K4 specific); IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0070577; F:lysine-acetylated histone binding; IDA:UniProtKB.
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:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0060216; P:definitive hemopoiesis; IEA:Ensembl.
DR GO; GO:0006306; P:DNA methylation; IEA:Ensembl.
DR GO; GO:0035162; P:embryonic hemopoiesis; TAS:UniProtKB.
DR GO; GO:0035640; P:exploration behavior; IEA:Ensembl.
DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0044648; P:histone H3-K4 dimethylation; IDA:CACAO.
DR GO; GO:0051568; P:histone H3-K4 methylation; IDA:UniProtKB.
DR GO; GO:0097692; P:histone H3-K4 monomethylation; IDA:CACAO.
DR GO; GO:0080182; P:histone H3-K4 trimethylation; IDA:BHF-UCL.
DR GO; GO:0043984; P:histone H4-K16 acetylation; IMP:UniProtKB.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl.
DR GO; GO:0051899; P:membrane depolarization; IEA:Ensembl.
DR GO; GO:1905642; P:negative regulation of DNA methylation; IMP:UniProtKB.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0018026; P:peptidyl-lysine monomethylation; IEA:Ensembl.
DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0032411; P:positive regulation of transporter activity; IMP:BHF-UCL.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR GO; GO:0071440; P:regulation of histone H3-K14 acetylation; ISS:UniProtKB.
DR GO; GO:1901674; P:regulation of histone H3-K27 acetylation; IEA:Ensembl.
DR GO; GO:2000615; P:regulation of histone H3-K9 acetylation; ISS:UniProtKB.
DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:0035864; P:response to potassium ion; IEA:Ensembl.
DR GO; GO:0048536; P:spleen development; IEA:Ensembl.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
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 DisProt; DP01116; -.
DR Gene3D; 1.20.920.10; -; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR Gene3D; 3.30.40.10; -; 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; IPR037927; KMT2A.
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; PTHR45838:SF2; 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 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; SSF47370; 1.
DR SUPFAM; SSF57903; SSF57903; 2.
DR SUPFAM; SSF82199; SSF82199; 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.
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 Isopeptide bond; Metal-binding; Methylation; Methyltransferase; Nucleus;
KW Phosphoprotein; Proto-oncogene; Reference proteome; Repeat;
KW S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW Transferase; Ubl conjugation; 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 1703..1748
FT /note="Bromo; divergent"
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 37..58
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..103
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 184..203
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 204..226
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 236..253
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 325..351
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 445..495
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 535..556
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 557..576
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 713..731
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 747..780
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 798..845
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 846..898
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1046..1061
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1249..1272
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1278..1302
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1303..1317
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1822..1847
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2096..2118
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2146..2174
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2189..2232
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2275..2320
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2402..2418
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2419..2445
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2526..2594
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2721..2746
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2747..2784
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2785..2821
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3011..3064
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3166..3183
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3195..3222
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3230..3244
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3464..3530
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3563..3606
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 2718-A--
FT 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 A-
FT 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 A-
FT 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 S-adenosyl-L-
FT 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 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 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 3809..3811
FT /evidence="ECO:0007829|PDB:2W5Y"
FT HELIX 3816..3820
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..3877
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"
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
