Q03164E9PQG7Q13743Q13744Q14845Q16364Q59FF2Q6UBD1Q9HBJ3Q9UD94Q9UMA3KMT2A_HUMANHistone-lysine N-methyltransferase 2ALysine N-methyltransferase 2A2.1.1.364ALL-1CXXC-type zinc finger protein 7Cysteine methyltransferase KMT2A2.1.1.-Myeloid/lymphoid or mixed-lineage leukemiaMyeloid/lymphoid or mixed-lineage leukemia protein 1Trithorax-like proteinZinc finger protein HRXMLL cleavage product N320N-terminal cleavage product of 320 kDap320MLL cleavage product C180C-terminal cleavage product of 180 kDap180KMT2AALL1CXXC7HRXHTRXMLLMLL1TRX1Homo sapiensHumanEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomoInvolvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)Exon/intron structure of the human ALL-1 (MLL) gene involved in translocations to chromosomal region 11q23 and acute leukaemias.NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3)VARIANT GLY-30NUCLEOTIDE SEQUENCE [GENOMIC DNA]VARIANTS VAL-53; LYS-502; THR-2319; ARG-2354; ARG-2387; ILE-3714 AND ALA-3773Human chromosome 11 DNA sequence and analysis including novel gene identification.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]Two distinct portions of LTG19/ENL at 19p13 are involved in t(11;19) leukemia.NUCLEOTIDE SEQUENCE [MRNA] OF 1-1909The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene.NUCLEOTIDE SEQUENCE [MRNA] OF 63-3969 (ISOFORM 3)CHROMOSOMAL TRANSLOCATION WITH AFF1/MLLT2Homo sapiens protein coding cDNA.NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 812-3969A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias.NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1112-1140 AND 1552-162NUCLEOTIDE SEQUENCE [MRNA] OF 1317-2328ERRATUM OF PUBMED:1303259Molecular analysis of the chromosomal breakpoint and fusion transcripts in the acute lymphoblastic SEM cell line with chromosomal translocation t(4;11).NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1212-1603 (ISOFORM 3)The human MLL gene: nucleotide sequence, homology to the Drosophila trx zinc-finger domain, and alternative splicing.NUCLEOTIDE SEQUENCE [MRNA] OF 1251-1654 (ISOFORM 2)Sequence analysis of the breakpoint cluster region in the ALL-1 gene involved in acute leukemia.NUCLEOTIDE SEQUENCE [MRNA] OF 1251-1538Detection of leukemia-associated MLL-GAS7 translocation early during chemotherapy with DNA topoisomerase II inhibitors.NUCLEOTIDE SEQUENCE [MRNA] OF 1311-1687 (ISOFORM 3)CHROMOSOMAL TRANSLOCATION WITH GAS7A method for identifying genes within yeast artificial chromosomes: application to isolation of MLL fusion cDNAs from acute leukaemia translocations.NUCLEOTIDE SEQUENCE [MRNA] OF 1421-1540Proteolytic cleavage of MLL generates a complex of N- and C-terminal fragments that confers protein stability and subnuclear localization.PROTEIN SEQUENCE OF 2719-2730CLEAVAGESUBUNITSUBCELLULAR LOCATIONMUTAGENESIS OF 2718-ASP--VAL-2720Fusion of the MLL gene with two different genes, AF-6 and AF-5alpha, by a complex translocation involving chromosomes 5, 6, 8 and 11 in infant leukemia.CHROMOSOMAL TRANSLOCATION WITH CENPKABI-1, a human homolog to mouse Abl-interactor 1, fuses the MLL gene in acute myeloid leukemia with t(10;11)(p11.2;q23).CHROMOSOMAL TRANSLOCATION WITH ABI1Association of SET domain and myotubularin-related proteins modulates growth control.INTERACTION WITH SBF1Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins.INTERACTION WITH PPP1R15ADISEASEFUNCTIONAF5q31, a newly identified AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia with ins(5;11)(q31;q13q23).CHROMOSOMAL TRANSLOCATION WITH AFF4Novel SH3 protein encoded by the AF3p21 gene is fused to the mixed lineage leukemia protein in a therapy-related leukemia with t(3;11)(p21;q23).CHROMOSOMAL TRANSLOCATION WITH NCKIPSD/AF3P21t(3;11) translocation in treatment-related acute myeloid leukemia fuses MLL with the GMPS (guanosine 5-prime monophosphate synthetase) gene.CHROMOSOMAL TRANSLOCATION WITH GMPSHuman LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23).CHROMOSOMAL TRANSLOCATION WITH LPPLCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23).CHROMOSOMAL TRANSLOCATION WITH TET1ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation.FUNCTIONCATALYTIC ACTIVITYTaspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene expression.CLEAVAGEINTERACTION WITH TASP1MUTAGENESIS OF 2666-ASP-GLY-2667 AND 2718-ASP--VAL-2720A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15.CHROMOSOMAL TRANSLOCATION WITH ZFYVE19 AND KNL1Characterization of the MLL partner gene AF15q14 involved in t(11;15)(q23;q14).CHROMOSOMAL TRANSLOCATION WITH KNL1Identification of a novel RAS GTPase-activating protein (RASGAP) gene at 9q34 as an MLL fusion partner in a patient with de novo acute myeloid leukemia.CHROMOSOMAL TRANSLOCATION WITH DAB2IPFLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line CNLBC1 derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23).CHROMOSOMAL TRANSLOCATION WITH SEPT11Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression.IDENTIFICATION IN THE MLL1/MLL COMPLEXAF4p12, a human homologue to the furry gene of Drosophila, as a novel MLL fusion partner.CHROMOSOMAL TRANSLOCATION WITH FRYLPhysical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF.FUNCTIONIDENTIFICATION IN THE MLL1/MLL COMPLEXINTERACTION WITH KAT8Nine-amino-acid transactivation domain: establishment and prediction utilities.DOMAIN 9AATADPTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex.IDENTIFICATION IN THE MLL1/MLL COMPLEXA quantitative atlas of mitotic phosphorylation.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-197; SER-518; SER-680; THR-840; SER-1056; THR-1845; SER-2098; THR-2147; SER-2151; THR-2525; SER-2955; SER-3036; THR-3372 AND SER-3511IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex.FUNCTIONCATALYTIC ACTIVITYCHARACTERIZATION OF THE MLL1/MLL COMPLEXINTERACTION WITH WDR5MUTAGENESIS OF ASN-3906 AND TYR-3942Large-scale proteomics analysis of the human kinome.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1858IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-2098 AND SER-3515IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Lysine acetylation targets protein complexes and co-regulates major cellular functions.ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-636; LYS-1130 AND LYS-1235IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153; SER-197; SER-926; SER-2955 AND THR-3372IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2201IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Quantitative dissection and stoichiometry determination of the human SET1/MLL histone methyltransferase complexes.IDENTIFICATION IN MLL1 COMPLEXScreen identifies bromodomain protein ZMYND8 in chromatin recognition of transcription-associated DNA damage that promotes homologous recombination.SUBCELLULAR LOCATIONBiochemical reconstitution and phylogenetic comparison of human SET1 family core complexes involved in histone methylation.FUNCTIONCATALYTIC ACTIVITYSUBUNITMUTAGENESIS OF ASN-3906De novo mutations in MLL cause Wiedemann-Steiner syndrome.INVOLVEMENT IN WDSTSMicrocephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation.INTERACTION WITH ZNF335Toward a comprehensive characterization of a human cancer cell phosphoproteome.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1858; SER-2098; THR-2525; SER-2611; SER-2796; SER-2955; SER-3036; SER-3511 AND SER-3527IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Automethylation activities within the mixed lineage leukemia-1 (MLL1) core complex reveal evidence supporting a 'two-active site' model for multiple histone H3 lysine 4 methylation.FUNCTIONCATALYTIC ACTIVITYBIOPHYSICOCHEMICAL PROPERTIESMETHYLATION AT CYS-3882MUTAGENESIS OF CYS-3882An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1837IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-2528IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]MLL1 is regulated by KSHV LANA and is important for virus latency.INTERACTION WITH HUMAN HERPESVIRUS 8/HHV-8 PROTEIN LANA1SUBCELLULAR LOCATIONSolution structure of the nonmethyl-CpG-binding CXXC domain of the leukaemia-associated MLL histone methyltransferase.STRUCTURE BY NMR OF 1146-1214 IN COMPLEX WITH ZINCDOMAIN CXXC-TYPE ZINC-FINGERDNA-BINDINGMUTAGENESIS OF ARG-1151; ARG-1153; ARG-1154; CYS-1155; CYS-1158; CYS-1161; GLN-1162; ASP-1166; CYS-1167; CYS-1170; ASN-1172; CYS-1173; ASP-1175; LYS-1176; 1178-LYS--GLY-1181; LYS-1178; PHE-1179; ASN-1183; LYS-1185; LYS-1186; GLN-1187; CYS-1188; CYS-1189; ARG-1192; LYS-1193; CYS-1194; GLN-1195 AND ASN-1196Structural basis for cooperative transcription factor binding to the CBP coactivator.STRUCTURE BY NMR OF 2842-2869 IN COMPLEX WITH CREBBPStructural basis for maintenance of unmethylated CpG elements by the CXXC domain of MLL and its critical contributions to MLL-AF9 immortalization activity.STRUCTURE BY NMR OF 1147-1203Structure of WDR5 bound to mixed lineage leukemia protein-1 peptide.X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 3764-3776 IN COMPLEX WITH WDR5INTERACTION WITH WDR5WDR5 interacts with mixed lineage leukemia (MLL) protein via the histone H3-binding pocket.X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 3764-3776 IN COMPLEX WITH WDR5INTERACTION WITH WDR5MUTAGENESIS OF ARG-3765 AND HIS-3769Structural basis for the requirement of additional factors for MLL1 SET domain activity and recognition of epigenetic marks.X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 3785-3969 IN COMPLEX WITH ZINC; S-ADENOSYL-L-HOMOCYSTEINE AND HISTONE H3 PEPTIDEFUNCTIONCATALYTIC ACTIVITYDOMAIN SETINTERACTION WITH ASH2L AND RBBP5MUTAGENESIS OF TYR-3858; GLN-3867; ASP-3869; ARG-3871; GLU-3872; TYR-3874; LYS-3878 AND TYR-3942The PHD3 domain of MLL acts as a CYP33-regulated switch between MLL-mediated activation and repression.STRUCTURE BY NMR OF 1564-1628 IN COMPLEX WITH ZINCFUNCTIONDOMAINMUTAGENESIS OF TRP-1594; VAL-1617 AND TYR-1619INTERACTION WITH PPIEPro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression.X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 1566-1784 IN COMPLEX WITH ZINC AND METHYLATED HISTONE H3INTERACTION WITH PPIEDOMAINMUTAGENESIS OF TYR-1581; GLN-1587 AND TRP-1594Structure of the MLL CXXC domain-DNA complex and its functional role in MLL-AF9 leukemia.STRUCTURE BY NMR OF 1147-1203 IN COMPLEX WITH ZINC AND TARGET DNAFUNCTIONDOMAIN CXXC-TYPE ZINC-FINGERMUTAGENESIS OF ARG-1150; ARG-1154; LYS-1185; GLN-1187; CYS-1188; LYS-1193; LEU-1197 AND MET-1200Structural and biochemical insights into MLL1 core complex assembly.X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 3761-3770 IN COMPLEX WITH RBBP5 AND WDR5FUNCTIONStructural insights into inhibition of the bivalent menin-MLL interaction by small molecules in leukemia.X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 6-15 IN COMPLEX WITH MEN1INTERACTION WITH MEN1INTERACTION OF FUSION PROTEIN KMT2A-MLLT3 WITH MEN1Structural basis for WDR5 interaction (Win) motif recognition in human SET1 family histone methyltransferases.X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 3755-3771 IN COMPLEX WITH WDR5INTERACTION WITH THE WRAD COMPLEXINTERACTION WITH WDR5MUTAGENESIS OF SER-3763; ARG-3765 AND HIS-3769MOTIF WINThe same pocket in menin binds both MLL and JUND but has opposite effects on transcription.X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 6-25 AND 103-153 IN COMPLEX WITH MEN1 AND PSIP1INTERACTION WITH MEN1INTERACTION OF KMT2A-MEN1 COMPLEX WITH PSIP1MOTIF MBMMUTAGENESIS OF ARG-6; TRP-7; ARG-8; PHE-9; PRO-10; ALA-11; ARG-12; PRO-13; ARG-24 AND ARG-25Allosteric communication in the KIX domain proceeds through dynamic repacking of the hydrophobic core.STRUCTURE BY NMR OF 2840-2858 IN COMPLEX WITH CREBBP AND CREB1The same site on the integrase-binding domain of lens epithelium-derived growth factor is a therapeutic target for MLL leukemia and HIV.STRUCTURE BY NMR OF 110-160 IN COMPLEX WITH PSIP1DOMAIN IBM MOTIFINTERACTION WITH PSIP1 AND MEN1INTERACTION OF FUSION PROTEIN KMT2A-MLLT3 WITH PSIP1 AND MEN1MUTAGENESIS OF PHE-129; PHE-148 AND LEU-149Validation and structural characterization of the LEDGF/p75-MLL interface as a new target for the treatment of MLL-dependent leukemia.STRUCTURE BY NMR OF 140-160 IN COMPLEX WITH PSIP1INTERACTION WITH PSIP1MUTAGENESIS OF PHE-129; PHE-133; GLU-144; GLU-146; PHE-148 AND PHE-151Structural basis for activity regulation of MLL family methyltransferases.X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 3813-3969 IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE AND ZINCFUNCTIONCATALYTIC ACTIVITYSUBUNITDOMAINMUTAGENESIS OF ASN-3861; ARG-3864 AND GLN-3867Design of a nanomolar affinity ligand to the KIX domain of CBP.X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 2839-2869Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase-dependent phosphorylation.STRUCTURE BY NMR OF 111-160 IN COMPLEX WITH PSIP1INTERACTION WITH PSIP1DOMAIN IBM MOTIFMUTAGENESIS OF VAL-132; PHE-133; SER-136 AND SER-142PHOSPHORYLATION AT SER-136; SER-142 AND SER-153DNA Sequence Recognition of Human CXXC Domains and Their Structural Determinants.X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF 1147-1204 IN COMPLEX WITH CPG DNADOMAIN CXXC-TYPE ZINC-FINGERZINC-BINDINGHistone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:24235145, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:25561738, PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20677832, PubMed:20010842). Promotes PPP1R15A-induced apoptosis (PubMed:10490642). Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-BMAL1 heterodimer (By similarity). Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-BMAL1 to chromatin (By similarity). Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145).L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = H(+) + N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteineN(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = H(+) + N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteineL-cysteinyl-[protein] + S-adenosyl-L-methionine = H(+) + S-adenosyl-L-homocysteine + S-methyl-L-cysteinyl-[protein]10.4 uM for S-adenosyl-L-methionine (for histone-lysine N-methyltransferase activity)6.5 uM for S-adenosyl-L-methionine (for protein-cysteine methyltransferase)MLL cleavage product N320 heterodimerizes with MLL cleavage product C180 (via SET and FYRC domains). Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, HCFC2, WDR5, DPY30 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (PubMed:15199122, PubMed:15960975, PubMed:17500065, PubMed:19556245, PubMed:23508102, PubMed:19187761, PubMed:26886794). Forms a core complex with the evolutionary conserved subcomplex WRAD composed of WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits; WRAD differentially stimulates the methyltransferase activity (PubMed:25561738). Interacts (via WIN motif) with WDR5; the interaction is direct (PubMed:19556245, PubMed:18829459, PubMed:22665483, PubMed:18840606). Interaction with WDR5 is required for stable interaction with ASH2L and RBBP5, and thereby also for optimal histone methyltransferase activity (PubMed:26886794). Interacts with KAT8/MOF; the interaction is direct (PubMed:15960975). Interacts with SBF1 and PPP1R15A (PubMed:9537414, PubMed:10490642). Interacts with ZNF335 (PubMed:23178126). Interacts with CLOCK and BMAL1 in a circadian manner (By similarity). Interacts with PPIE; this results in decreased histone H3 methyltransferase activity (PubMed:20677832, PubMed:20541251). Interacts with CREBBP (PubMed:16253272). Interacts with the WRAD complex composed of WDR5, RBBP5, ASH2L and DPY30 (PubMed:22665483). Interacts (via MBM motif) with MEN1 (PubMed:22936661, PubMed:22327296, PubMed:25305204). Interacts (via IBM motifs) with PSIP1 (via IBD domain) with moderate affinity whereas the KMT2A-MEN1 complex interacts with a greater affinity; MEN1 enhances interaction of KMT2A with PSIP1 (PubMed:22327296, PubMed:25305204, PubMed:25082813, PubMed:29997176). Phosphorylation increases its affinity for PSIP1 (PubMed:29997176). Forms a complex with CREBBP and CREB1 (PubMed:23651431).(Microbial infection) Interacts with herpes virus 8/HHV-8 protein LANA1; this interaction regulates the MLL1 histone methyltransferase activity on viral DNA.Q03164P10275false4Q03164Q9UBL3-3false4Q03164Q6P1J9false4Q03164Q6PD62false5Q03164P68431false11Q03164Q9H7Z6false3Q03164Q03164false5Q03164O00255-2false12Q03164Q8N7H5false4Q03164Q9UNP9false4Q03164Q15291false9Q03164Q96EB6false5Q03164Q13309-1false2Q03164P61964false13Q03164Q9WTL8true3Q03164O08785true3Q03164P45481true7PRO_0000390949Q02548false2PRO_0000390950Q92794false10PRO_0000390950P61964false2NucleusMLL cleavage product N320NucleusMLL cleavage product C180NucleusLocalizes to a diffuse nuclear pattern when not associated with MLL cleavage product N320.Q03164-11Q03164-2214P-18BQ03164-33Heart, lung, brain and T- and B-lymphocytes.The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.The SET domain structure is atypical and is not in an optimal position to have methyltransferase activity. It requires other components of the MLL1/MLL complex, such as ASH2L or RBBP5, to order the active site and obtain optimal histone methyltransferase activity.The CXXC-type zinc finger binds to DNA sequence elements containing unnmethylated CpG dinucleotides.The third PHD-type zinc-finger binds both trimethylated histone H3K4me3 and PPIE; histone and PPIE bind to distinct surfaces (PubMed:20677832, PubMed:20541251). Nevertheless, PPIE binding and histone binding are mutually inhibitory (PubMed:20677832). Isomerization of a peptidylproline bond in the linker between the third PHD-type zinc-finger and the bromo domain disrupts the interaction between the bromo domain and the third PHD-type zinc-finger, and thereby facilitates interaction with PPIE (PubMed:20541251).Proteolytic cleavage by TASP1 generates MLL cleavage product N320 and MLL cleavage product C180, which reassemble through a non-covalent association. 2 cleavage sites exist, cleavage site 1 (CS1) and cleavage site 2 (CS2), to generate MLL cleavage products N320 and C180. CS2 is the major site.Phosphorylation increases its interaction with PSIP1.Auto-methylated at Cys-3882: auto-methylation is inhibited by the WRAD complex and unmodified histone H3.Wiedemann-Steiner syndrome
WDSTS
A syndrome characterized by hairy elbows (hypertrichosis cubiti), intellectual disability, a distinctive facial appearance, and short stature. Facial characteristics include long eyelashes, thick or arched eyebrows with a lateral flare, and downslanting and vertically narrow palpebral fissures.The disease is caused by variants affecting the gene represented in this entry.Chromosomal aberrations involving KMT2A are a cause of acute leukemias. Translocation t(1;11)(q21;q23) with MLLT11/AF1Q; translocation t(3;11)(p21;q23) with NCKIPSD/AF3p21; translocation t(3,11)(q25,q23) with GMPS; translocation t(4;11)(q21;q23) with AFF1/MLLT2/AF4; insertion ins(5;11)(q31;q13q23) with AFF4/AF5Q31; translocation t(5;11)(q12;q23) with AF5-alpha/CENPK; translocation t(6;11)(q27;q23) with AFDN; translocation t(9;11)(p22;q23) with MLLT3/AF9; translocation t(10;11)(p11.2;q23) with ABI1; translocation t(10;11)(p12;q23) with MLLT10/AF10; t(11;15)(q23;q14) with KNL1 and ZFYVE19; translocation t(11;17)(q23;q21) with MLLT6/AF17; translocation t(11;19)(q23;p13.3) with ELL; translocation t(11;19)(q23;p13.3) with MLLT1/ENL; translocation t(11;19)(q23;p23) with GAS7; translocation t(X;11)(q13;q23) with FOXO4/AFX1. Translocation t(3;11)(q28;q23) with LPP. Translocation t(10;11)(q22;q23) with TET1. Translocation t(9;11)(q34;q23) with DAB2IP. Translocation t(4;11)(p12;q23) with FRYL. Fusion proteins KMT2A-MLLT1, KMT2A-MLLT3 and KMT2A-ELL interact with PPP1R15A and, on the contrary to unfused KMT2A, inhibit PPP1R15A-induced apoptosis. Fusion protein KMT2A-MLLT3 interacts with MEN1 and PSIP1 (PubMed:22936661, PubMed:25305204).A chromosomal aberration involving KMT2A may be a cause of chronic neutrophilic leukemia. Translocation t(4;11)(q21;q23) with SEPT11.Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily.Contaminating sequence. Potential poly-A sequence.3D-structureAcetylationAlternative splicingApoptosisBiological rhythmsBromodomainChromatin regulatorChromosomal rearrangementDirect protein sequencingDNA-bindingHost-virus interactionIsopeptide bondMetal-bindingMethylationMethyltransferaseNucleusPhosphoproteinProto-oncogeneReference proteomeRepeatS-adenosyl-L-methionineTranscriptionTranscription regulationTransferaseUbl conjugationZincZinc-fingerZn(2+)Zn(2+)Zn(2+)Zn(2+)Zn(2+)Zn(2+)Zn(2+)Zn(2+)S-adenosyl-L-methionineS-adenosyl-L-methionineS-adenosyl-L-methionineS-adenosyl-L-methionineZn(2+)Zn(2+)S-adenosyl-L-methionineZn(2+)Zn(2+)SSGTEAGAVEKQPSTPRQRVISARAWARAFAFHYPAARRAPAREREFAVAFASDSDEQEQFALAFARARARARACACACAQADACACANACADAKAKFGGAAAAKAFANAKAKAQACACDCARAKACAQANALAMAYAQAWAWEVAYADGAADGVAAASARAHAFHYYAYFNINTRAQAQLQVDARAEAYAKACASNAYAFYFEELTTQIPCSWRTKGHIHDKKTEPFRLLAWSWCLNQEVARGQRPLNTEGSCQHPSKNRGNDDGARMAHSCRWRFPARPGTTGGGGGGGRRGLGGAPRQRVPALLLPPGPPVGGGGPGAPPSPPAVAAAAAAAGSSGAGVPGGAAAASAASSSSASSSSSSSSSASSGPALLRVGPGFDAALQVSAAIGTNLRRFRAVFGESGGGGGSGEDEQFLGFGSDEEVRVRSPTRSPSVKTSPRKPRGRPRSGSDRNSAILSDPSVFSPLNKSETKSGDKIKKKDSKSIEKKRGRPPTFPGVKIKITHGKDISELPKGNKEDSLKKIKRTPSATFQQATKIKKLRAGKLSPLKSKFKTGKLQIGRKGVQIVRRRGRPPSTERIKTPSGLLINSELEKPQKVRKDKEGTPPLTKEDKTVVRQSPRRIKPVRIIPSSKRTDATIAKQLLQRAKKGAQKKIEKEAAQLQGRKVKTQVKNIRQFIMPVVSAISSRIIKTPRRFIEDEDYDPPIKIARLESTPNSRFSAPSCGSSEKSSAASQHSSQMSSDSSRSSSPSVDTSTDSQASEEIQVLPEERSDTPEVHPPLPISQSPENESNDRRSRRYSVSERSFGSRTTKKLSTLQSAPQQQTSSSPPPPLLTPPPPLQPASSISDHTPWLMPPTIPLASPFLPASTAPMQGKRKSILREPTFRWTSLKHSRSEPQYFSSAKYAKEGLIRKPIFDNFRPPPLTPEDVGFASGFSASGTAASARLFSPLHSGTRFDMHKRSPLLRAPRFTPSEAHSRIFESVTLPSNRTSAGTSSSGVSNRKRKRKVFSPIRSEPRSPSHSMRTRSGRLSSSELSPLTPPSSVSSSLSISVSPLATSALNPTFTFPSHSLTQSGESAEKNQRPRKQTSAPAEPFSSSSPTPLFPWFTPGSQTERGRNKDKAPEELSKDRDADKSVEKDKSRERDREREKENKRESRKEKRKKGSEIQSSSALYPVGRVSKEKVVGEDVATSSSAKKATGRKKSSSHDSGTDITSVTLGDTTAVKTKILIKKGRGNLEKTNLDLGPTAPSLEKEKTLCLSTPSSSTVKHSTSSIGSMLAQADKLPMTDKRVASLLKKAKAQLCKIEKSKSLKQTDQPKAQGQESDSSETSVRGPRIKHVCRRAAVALGRKRAVFPDDMPTLSALPWEEREKILSSMGNDDKSSIAGSEDAEPLAPPIKPIKPVTRNKAPQEPPVKKGRRSRRCGQCPGCQVPEDCGVCTNCLDKPKFGGRNIKKQCCKMRKCQNLQWMPSKAYLQKQAKAVKKKEKKSKTSEKKDSKESSVVKNVVDSSQKPTPSAREDPAPKKSSSEPPPRKPVEEKSEEGNVSAPGPESKQATTPASRKSSKQVSQPALVIPPQPPTTGPPRKEVPKTTPSEPKKKQPPPPESGPEQSKQKKVAPRPSIPVKQKPKEKEKPPPVNKQENAGTLNILSTLSNGNSSKQKIPADGVHRIRVDFKEDCEAENVWEMGGLGILTSVPITPRVVCFLCASSGHVEFVYCQVCCEPFHKFCLEENERPLEDQLENWCCRRCKFCHVCGRQHQATKQLLECNKCRNSYHPECLGPNYPTKPTKKKKVWICTKCVRCKSCGSTTPGKGWDAQWSHDFSLCHDCAKLFAKGNFCPLCDKCYDDDDYESKMMQCGKCDRWVHSKCENLSDEMYEILSNLPESVAYTCVNCTERHPAEWRLALEKELQISLKQVLTALLNSRTTSHLLRYRQAAKPPDLNPETEESIPSRSSPEGPDPPVLTEVSKQDDQQPLDLEGVKRKMDQGNYTSVLEFSDDIVKIIQAAINSDGGQPEIKKANSMVKSFFIRQMERVFPWFSVKKSRFWEPNKVSSNSGMLPNAVLPPSLDHNYAQWQEREENSHTEQPPLMKKIIPAPKPKGPGEPDSPTPLHPPTPPILSTDRSREDSPELNPPPGIEDNRQCALCLTYGDDSANDAGRLLYIGQNEWTHVNCALWSAEVFEDDDGSLKNVHMAVIRGKQLRCEFCQKPGATVGCCLTSCTSNYHFMCSRAKNCVFLDDKKVYCQRHRDLIKGEVVPENGFEVFRRVFVDFEGISLRRKFLNGLEPENIHMMIGSMTIDCLGILNDLSDCEDKLFPIGYQCSRVYWSTTDARKRCVYTCKIVECRPPVVEPDINSTVEHDENRTIAHSPTSFTESSSKESQNTAEIISPPSPDRPPHSQTSGSCYYHVISKVPRIRTPSYSPTQRSPGCRPLPSAGSPTPTTHEIVTVGDPLLSSGLRSIGSRRHSTSSLSPQRSKLRIMSPMRTGNTYSRNNVSSVSTTGTATDLESSAKVVDHVLGPLNSSTSLGQNTSTSSNLQRTVVTVGNKNSHLDGSSSSEMKQSSASDLVSKSSSLKGEKTKVLSSKSSEGSAHNVAYPGIPKLAPQVHNTTSRELNVSKIGSFAEPSSVSFSSKEALSFPHLHLRGQRNDRDQHTDSTQSANSSPDEDTEVKTLKLSGMSNRSSIINEHMGSSSRDRRQKGKKSCKETFKEKHSSKSFLEPGQVTTGEEGNLKPEFMDEVLTPEYMGQRPCNNVSSDKIGDKGLSMPGVPKAPPMQVEGSAKELQAPRKRTVKVTLTPLKMENESQSKNALKESSPASPLQIESTSPTEPISASENPGDGPVAQPSPNNTSCQDSQSNNYQNLPVQDRNLMLPDGPKPQEDGSFKRRYPRRSARARSNMFFGLTPLYGVRSYGEEDIPFYSSSTGKKRGKRSAEGQVDGADDLSTSDEDDLYYYNFTRTVISSGGEERLASHNLFREEEQCDLPKISQLDGVDDGTESDTSVTATTRKSSQIPKRNGKENGTENLKIDRPEDAGEKEHVTKSSVGHKNEPKMDNCHSVSRVKTQGQDSLEAQLSSLESSRRVHTSTPSDKNLLDTYNTELLKSDSDNNNSDDCGNILPSDIMDFVLKNTPSMQALGESPESSSSELLNLGEGLGLDSNREKDMGLFEVFSQQLPTTEPVDSSVSSSISAEEQFELPLELPSDLSVLTTRSPTVPSQNPSRLAVISDSGEKRVTITEKSVASSESDPALLSPGVDPTPEGHMTPDHFIQGHMDADHISSPPCGSVEQGHGNNQDLTRNSSTPGLQVPVSPTVPIQNQKYVPNSTDSPGPSQISNAAVQTTPPHLKPATEKLIVVNQNMQPLYVLQTLPNGVTQKIQLTSSVSSTPSVMETNTSVLGPMGGGLTLTTGLNPSLPTSQSLFPSASKGLLPMSHHQHLHSFPAATQSSFPPNISNPPSGLLIGVQPPPDPQLLVSESSQRTDLSTTVATPSSGLKKRPISRLQTRKNKKLAPSSTPSNIAPSDVVSNMTLINFTPSQLPNHPSLLDLGSLNTSSHRTVPNIIKRSKSSIMYFEPAPLLPQSVGGTAATAAGTSTISQDTSHLTSGSVSGLASSSSVLNVVSMQTTTTPTSSASVPGHVTLTNPRLLGTPDIGSISNLLIKASQQSLGIQDQPVALPPSSGMFPQLGTSQTPSTAAITAASSICVLPSTQTTGITAASPSGEADEHYQLQHVNQLLASKTGIHSSQRDLDSASGPQVSNFTQTVDAPNSMGLEQNKALSSAVQASPTSPGGSPSSPSSGQRSASPSVPGPTKPKPKTKRFQLPLDKGNGKKHKVSHLRTSSSEAHIPDQETTSLTSGTGTPGAEAEQQDTASVEQSSQKECGQPAGQVAVLPEVQVTQNPANEQESAEPKTVEEEESNFSSPLMLWLQQEQKRKESITEKKPKKGLVFEISSDDGFQICAESIEDAWKSLTDKVQEARSNARLKQLSFAGVNGLRMLGILHDAVVFLIEQLSGAKHCRNYKFRFHKPEEANEPPLNPHGSARAEVHLRKSAFDMFNFLASKHRQPPEYNPNDEEEEEVQLKSARRATSMDLPMPMRFRHLKKTSKEAVGVYRSPIHGRGLFCKRNIDAGEMVIEYAGNVIRSIQTDKREKYYDSKGIGCYMFRIDDSEVVDATMHGNAARFINHSCEPNCYSRVINIDGQKHIVIFAMRKIYRGEELTYDYKFPIEDASNKLPCNCGAKKCRKFLN
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