UniProtKB - Q03164 (KMT2A_HUMAN)
Histone-lysine N-methyltransferase 2A
KMT2A
Functioni
Histone 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-ARNTL/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-ARNTL/BMAL1 to chromatin (By similarity).
Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145).
By similarity1 Publication9 PublicationsCatalytic activityi
- L-lysyl4-[histone H3] + S-adenosyl-L-methionine = H+ + N6-methyl-L-lysyl4-[histone H3] + S-adenosyl-L-homocysteine6 PublicationsEC:2.1.1.3646 PublicationsThis reaction proceeds in the forward2 Publications direction.
- N6-methyl-L-lysyl4-[histone H3] + S-adenosyl-L-methionine = H+ + N6,N6-dimethyl-L-lysyl4-[histone H3] + S-adenosyl-L-homocysteine4 PublicationsThis reaction proceeds in the forward1 Publication direction.
- L-cysteinyl-[protein] + S-adenosyl-L-methionine = H+ + S-adenosyl-L-homocysteine + S-methyl-L-cysteinyl-[protein]1 PublicationThis reaction proceeds in the forward1 Publication direction.
Kineticsi
- KM=10.4 µM for S-adenosyl-L-methionine (for histone-lysine N-methyltransferase activity)1 Publication
- KM=6.5 µM for S-adenosyl-L-methionine (for protein-cysteine methyltransferase)1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 1155 | Zinc 1PROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Metal bindingi | 1158 | Zinc 1PROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Metal bindingi | 1161 | Zinc 1PROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Metal bindingi | 1167 | Zinc 2PROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Metal bindingi | 1170 | Zinc 2PROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Metal bindingi | 1173 | Zinc 2PROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Metal bindingi | 1189 | Zinc 2PROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Metal bindingi | 1194 | Zinc 1PROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Sitei | 3765 | Important for WDR5-recognition and binding1 Publication | 1 | |
Binding sitei | 3839 | S-adenosyl-L-methioninePROSITE-ProRule annotationCombined sources2 Publications | 1 | |
Binding sitei | 3841 | S-adenosyl-L-methioninePROSITE-ProRule annotationCombined sources2 Publications | 1 | |
Binding sitei | 3883 | S-adenosyl-L-methioninePROSITE-ProRule annotationCombined sources2 Publications | 1 | |
Metal bindingi | 3909 | ZincCombined sources2 Publications | 1 | |
Metal bindingi | 3957 | ZincCombined sources2 Publications | 1 | |
Binding sitei | 3958 | S-adenosyl-L-methioninePROSITE-ProRule annotationCombined sources2 Publications | 1 | |
Metal bindingi | 3959 | ZincCombined sources2 Publications | 1 | |
Metal bindingi | 3964 | ZincCombined sources2 Publications | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 169 – 180 | A.T hook 1Add BLAST | 12 | |
DNA bindingi | 217 – 227 | A.T hook 2Add BLAST | 11 | |
DNA bindingi | 301 – 309 | A.T hook 3 | 9 | |
Zinc fingeri | 1147 – 1195 | CXXC-typePROSITE-ProRule annotation1 PublicationAdd BLAST | 49 | |
Zinc fingeri | 1431 – 1482 | PHD-type 1PROSITE-ProRule annotationAdd BLAST | 52 | |
Zinc fingeri | 1479 – 1533 | PHD-type 2PROSITE-ProRule annotationAdd BLAST | 55 | |
Zinc fingeri | 1566 – 1627 | PHD-type 3PROSITE-ProRule annotationAdd BLAST | 62 | |
Zinc fingeri | 1870 – 1910 | C2HC pre-PHD-typePROSITE-ProRule annotationAdd BLAST | 41 | |
Zinc fingeri | 1931 – 1978 | PHD-type 4PROSITE-ProRule annotationAdd BLAST | 48 |
GO - Molecular functioni
- histone methyltransferase activity (H3-K4 specific) Source: UniProtKB
- identical protein binding Source: IntAct
- lysine-acetylated histone binding Source: UniProtKB
- minor groove of adenine-thymine-rich DNA binding Source: UniProtKB
- protein-cysteine methyltransferase activity Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
- unmethylated CpG binding Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- chromatin organization Source: UniProtKB-KW
- circadian regulation of gene expression Source: UniProtKB
- embryonic hemopoiesis Source: UniProtKB
- histone H3-K4 dimethylation Source: CACAO
- histone H3-K4 methylation Source: UniProtKB
- histone H3-K4 monomethylation Source: CACAO
- histone H3-K4 trimethylation Source: BHF-UCL
- histone H4-K16 acetylation Source: UniProtKB
- negative regulation of DNA methylation Source: UniProtKB
- positive regulation of histone H3-K4 methylation Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- positive regulation of transporter activity Source: BHF-UCL
- protein-containing complex assembly Source: UniProtKB
- regulation of histone H3-K14 acetylation Source: UniProtKB
- regulation of histone H3-K9 acetylation Source: UniProtKB
Keywordsi
Molecular function | Chromatin regulator, DNA-binding, Methyltransferase, Transferase |
Biological process | Apoptosis, Biological rhythms, Transcription, Transcription regulation |
Ligand | Metal-binding, S-adenosyl-L-methionine, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q03164 |
Reactomei | R-HSA-3214841, PKMTs methylate histone lysines R-HSA-8936459, RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function R-HSA-8939236, RUNX1 regulates transcription of genes involved in differentiation of HSCs R-HSA-9616222, Transcriptional regulation of granulopoiesis |
SignaLinki | Q03164 |
SIGNORi | Q03164 |
Names & Taxonomyi
Protein namesi | Recommended name: Histone-lysine N-methyltransferase 2A (EC:2.1.1.3646 Publications)Short name: Lysine N-methyltransferase 2A Alternative name(s): ALL-11 Publication CXXC-type zinc finger protein 7 Cysteine methyltransferase KMT2ACurated (EC:2.1.1.-1 Publication) Myeloid/lymphoid or mixed-lineage leukemia Myeloid/lymphoid or mixed-lineage leukemia protein 1 Trithorax-like protein Zinc finger protein HRX Cleaved into the following 2 chains: Alternative name(s): N-terminal cleavage product of 320 kDa Short name: p320 Alternative name(s): C-terminal cleavage product of 180 kDa Short name: p180 |
Gene namesi | Name:KMT2A Synonyms:ALL1, CXXC7, HRX, HTRX, MLL, MLL1, TRX1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:7132, KMT2A |
MIMi | 159555, gene+phenotype |
neXtProti | NX_Q03164 |
VEuPathDBi | HostDB:ENSG00000118058 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Nucleus
Note: Localizes to a diffuse nuclear pattern when not associated with MLL cleavage product N320.
Cytosol
- cytosol Source: HPA
Nucleus
- histone methyltransferase complex Source: UniProtKB
- MLL1 complex Source: UniProtKB
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Involvement in diseasei
Wiedemann-Steiner syndrome (WDSTS)1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 6 | R → A: Reduced interaction with MEN1. 1 Publication | 1 | |
Mutagenesisi | 7 | W → A: Reduced interaction with MEN1. 1 Publication | 1 | |
Mutagenesisi | 8 | R → A: Reduced interaction with MEN1. 1 Publication | 1 | |
Mutagenesisi | 9 | F → A: Loss of interaction with MEN1. 1 Publication | 1 | |
Mutagenesisi | 9 | F → H or Y: Reduced interaction with MEN1. 1 Publication | 1 | |
Mutagenesisi | 10 | P → A: Reduced interaction with MEN1. 1 Publication | 1 | |
Mutagenesisi | 11 | A → R: Reduced interaction with MEN1. 1 Publication | 1 | |
Mutagenesisi | 12 | R → A: Reduced interaction with MEN1. 1 Publication | 1 | |
Mutagenesisi | 13 | P → A: Reduced interaction with MEN1. 1 Publication | 1 | |
Mutagenesisi | 24 | R → E: Reduced interaction with MEN1; when associated with E-25. 1 Publication | 1 | |
Mutagenesisi | 25 | R → E: Reduced interaction with MEN1; when associated with E-24. 1 Publication | 1 | |
Mutagenesisi | 129 | F → A: Weakly affects interaction with PSIP1 whereas significantly decreases interaction of KMT2A-MEN1 complex with PSIP1. Reduced interaction with PSIP1; when associated with A-133. 2 Publications | 1 | |
Mutagenesisi | 132 | V → A: Reduced interaction with PSIP1; when associated with A-133. 1 Publication | 1 | |
Mutagenesisi | 133 | F → A: Reduced interaction with PSIP1; when associated with A-129 or A-132. 2 Publications | 1 | |
Mutagenesisi | 136 | S → D: Phosphomimetic mutant. Significant increase in interaction with PSIP1; when associated with D-142. 1 Publication | 1 | |
Mutagenesisi | 142 | S → D: Phosphomimetic mutant. Significant increase in interaction with PSIP1; when associated with D-136. 1 Publication | 1 | |
Mutagenesisi | 144 | E → Q: Loss of interaction with PSIP1; when associated with Q-146 and A-148. 1 Publication | 1 | |
Mutagenesisi | 146 | E → Q: Loss of interaction with PSIP1; when associated with Q-144 and A-148. 1 Publication | 1 | |
Mutagenesisi | 148 | F → A: Reduced interaction with PSIP1. Loss of interaction with PSIP1; when associated with A-149 or Q-144 and Q-146. 2 Publications | 1 | |
Mutagenesisi | 149 | L → A: Loss of interaction with PSIP1; when associated with A-148. 1 Publication | 1 | |
Mutagenesisi | 151 | F → A: Reduced interaction with PSIP1. 1 Publication | 1 | |
Mutagenesisi | 1150 | R → A: Impairs DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1151 | R → A: Impairs DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1153 | R → A: No effect on stability or DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1154 | R → A: Impairs DNA-binding. 2 Publications | 1 | |
Mutagenesisi | 1155 | C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1158 | C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1161 | C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1162 | Q → A: No effect on stability or DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1166 | D → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1167 | C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1170 | C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1172 | N → A: No effect on stability or DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1173 | C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1175 | D → A: Impairs DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1176 | K → A: Impairs DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1178 – 1181 | KFGG → AAAA: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication | 4 | |
Mutagenesisi | 1178 | K → A: Impairs DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1179 | F → A: Impairs DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1183 | N → A: Impairs DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1185 | K → A: Impairs DNA-binding. 2 Publications | 1 | |
Mutagenesisi | 1186 | K → A: Impairs DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1187 | Q → A: Impairs DNA-binding. 2 Publications | 1 | |
Mutagenesisi | 1188 | C → A: No effect on stability or DNA-binding. 2 Publications | 1 | |
Mutagenesisi | 1188 | C → D: Abolishes DNA-binding and increases CpG methylation of the HOXA9 promoter region. Does not lead to the development of leukemia when overexpressed in mice as gene fusion with MLLT3. 1 Publication | 1 | |
Mutagenesisi | 1189 | C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1192 | R → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1193 | K → A: Impairs DNA-binding. 2 Publications | 1 | |
Mutagenesisi | 1194 | C → A: Impairs zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1195 | Q → A: No effect on stability or DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1196 | N → A: No effect on stability or DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1197 | L → A: Mildly decreases DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1200 | M → A: No effect on DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 1581 | Y → A: Decreases affinity for histone H3K4me3. 1 Publication | 1 | |
Mutagenesisi | 1587 | Q → A: Decreases affinity for histone H3K4me3. 1 Publication | 1 | |
Mutagenesisi | 1594 | W → A: Abolishes interaction with histone H3K4me3. 1 Publication | 1 | |
Mutagenesisi | 1594 | W → E: Decreases affinity for histone H3K4me3. 1 Publication | 1 | |
Mutagenesisi | 1617 | V → A: Decreases binding affinity for PPIE. 1 Publication | 1 | |
Mutagenesisi | 1619 | Y → A: May perturb protein folding and thereby decrease binding affinity for PPIE. 1 Publication | 1 | |
Mutagenesisi | 2666 – 2667 | DG → AA: Reduces cleavage without abolishing it. Abolishes cleavage by TASP1; when associated with 2718-A--A-2720. 1 Publication | 2 | |
Mutagenesisi | 2718 – 2720 | DGV → AAA: Abolishes cleavage by TASP1; when associated with 2666-A-A-2667. 2 Publications | 3 | |
Mutagenesisi | 3763 | S → A: Increased interaction with WDR5. 1 Publication | 1 | |
Mutagenesisi | 3765 | R → A: Loss of interaction with the WRAD complex and WDR5. 2 Publications | 1 | |
Mutagenesisi | 3769 | H → A or F: Slight decrease in interaction with WDR5. 1 Publication | 1 | |
Mutagenesisi | 3769 | H → Y: Increased interaction with WDR5. 1 Publication | 1 | |
Mutagenesisi | 3858 | Y → A: Impairs methyltransferase activity toward unmodified or monomethylated H3K4me. 1 Publication | 1 | |
Mutagenesisi | 3858 | Y → F: Slightly affects methyltransferase activity toward unmodified or monomethylated H3K4me. 1 Publication | 1 | |
Mutagenesisi | 3861 | N → I: Leads to stable interaction with ASH2L and RBBP5 in the absence of WDR5; when associated with L-3867. 1 Publication | 1 | |
Mutagenesisi | 3861 | N → T: Leads to stable interaction with ASH2L and RBBP5 in the absence of WDR5; when associated with V-3867. 1 Publication | 1 | |
Mutagenesisi | 3864 | R → A: Disrupts interaction with ASH2L and RBBP5 and nearly abolishes histone methyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 3867 | Q → A: Slightly affects methyltransferase activity of the enzyme alone, while it impairs methyltransferase activity in complex; when associated with A-3871. 1 Publication | 1 | |
Mutagenesisi | 3867 | Q → L: Leads to stable interaction with ASH2L and RBBP5 in the absence of WDR5; when associated with I-3861. 1 Publication | 1 | |
Mutagenesisi | 3867 | Q → V: Leads to stable interaction with ASH2L and RBBP5 in the absence of WDR5; when associated with T-3861. 1 Publication | 1 | |
Mutagenesisi | 3869 | D → A: Does not affect methyltransferase activity of the enzyme alone or in complex; when associated with A-3872. 1 Publication | 1 | |
Mutagenesisi | 3871 | R → A: Slightly affects methyltransferase activity of the enzyme alone, while it impairs methyltransferase activity in complex; when associated with A-3867. 1 Publication | 1 | |
Mutagenesisi | 3872 | E → A: Does not affect methyltransferase activity of the enzyme alone or in complex; when associated with A-3869. 1 Publication | 1 | |
Mutagenesisi | 3874 | Y → A: Affects methyltransferase activity of the enzyme alone, while it does not affect methyltransferase activity in complex; when associated with A-3878. 1 Publication | 1 | |
Mutagenesisi | 3878 | K → A: Affects methyltransferase activity of the enzyme alone, while it does not affect methyltransferase activity in complex; when associated with A-3874. 1 Publication | 1 | |
Mutagenesisi | 3882 | C → A or S: Abolished auto-methylation. 1 Publication | 1 | |
Mutagenesisi | 3906 | N → A: Loss of the histone H3 methyltransferase activity. Abolishes interaction with S-adenosyl-L-methionine. 2 Publications | 1 | |
Mutagenesisi | 3942 | Y → A or F: Impairs methyltransferase activity toward unmodified or monomethylated H3K4me. 2 Publications | 1 | |
Mutagenesisi | 3942 | Y → F: Shifts from a specific monomethyltransferase to a di- and trimethyltransferase activity. 2 Publications | 1 |
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 1334 – 1335 | Breakpoint for translocation to form KMT2A-ZFYVE19 oncogene | 2 | |
Sitei | 1362 – 1363 | Breakpoint for translocation to form KMT2A-AF3P21 and KMT2A-KNL1 oncogenes | 2 | |
Sitei | 1362 – 1363 | Breakpoint for translocation to form KMT2A-CENPK oncogene | 2 | |
Sitei | 1362 | Breakpoint for translocation to form KMT2A-FRYL fusion protein | 1 | |
Sitei | 1406 – 1407 | Breakpoint for translocation to form KMT2A-AFF4 fusion protein | 2 | |
Sitei | 1444 – 1445 | Breakpoint for translocation to form KMT2A-GAS7 oncogene | 2 | |
Sitei | 1444 – 1445 | Breakpoint for translocation to form KMT2A-LPP | 2 |
Keywords - Diseasei
Proto-oncogeneOrganism-specific databases
DisGeNETi | 4297 |
MalaCardsi | KMT2A |
MIMi | 159555, gene+phenotype 605130, phenotype |
OpenTargetsi | ENSG00000118058 |
Orphaneti | 98831, Acute myeloid leukemia with 11q23 abnormalities 402017, Acute myeloid leukemia with t(9;11)(p22;q23) 98835, Acute undifferentiated leukemia 530995, Mixed phenotype acute leukemia 99860, Precursor B-cell acute lymphoblastic leukemia 319182, Wiedemann-Steiner syndrome |
PharmGKBi | PA241 |
Miscellaneous databases
Pharosi | Q03164, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1293299 |
Genetic variation databases
BioMutai | KMT2A |
DMDMi | 146345435 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000124876 | 1 – 3969 | Histone-lysine N-methyltransferase 2AAdd BLAST | 3969 | |
ChainiPRO_0000390949 | 1 – 2718 | MLL cleavage product N3202 PublicationsAdd BLAST | 2718 | |
ChainiPRO_0000390950 | 2719 – 3969 | MLL cleavage product C1802 PublicationsAdd BLAST | 1251 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 136 | Phosphoserine; by CK21 Publication | 1 | |
Modified residuei | 142 | Phosphoserine; by CK21 Publication | 1 | |
Modified residuei | 153 | PhosphoserineCombined sources1 Publication | 1 | |
Modified residuei | 197 | PhosphoserineCombined sources | 1 | |
Modified residuei | 239 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 373 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 518 | PhosphoserineCombined sources | 1 | |
Modified residuei | 636 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 680 | PhosphoserineCombined sources | 1 | |
Modified residuei | 840 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 926 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1056 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1130 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 1235 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 1837 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1845 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 1858 | PhosphoserineCombined sources | 1 | |
Modified residuei | 2098 | PhosphoserineCombined sources | 1 | |
Modified residuei | 2147 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 2151 | PhosphoserineCombined sources | 1 | |
Modified residuei | 2201 | PhosphoserineCombined sources | 1 | |
Modified residuei | 2525 | PhosphothreonineCombined sources | 1 | |
Cross-linki | 2528 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 2611 | PhosphoserineCombined sources | 1 | |
Modified residuei | 2796 | PhosphoserineCombined sources | 1 | |
Modified residuei | 2955 | PhosphoserineCombined sources | 1 | |
Modified residuei | 2958 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 3036 | PhosphoserineCombined sources | 1 | |
Modified residuei | 3372 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 3462 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 3511 | PhosphoserineCombined sources | 1 | |
Modified residuei | 3515 | PhosphoserineCombined sources | 1 | |
Modified residuei | 3527 | PhosphoserineCombined sources | 1 | |
Modified residuei | 3882 | S-methylcysteine; by autocatalysis1 Publication | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 2666 – 2667 | Cleavage; by TASP1, site 11 Publication | 2 | |
Sitei | 2718 – 2719 | Cleavage; by TASP1, site 21 Publication | 2 |
Keywords - PTMi
Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q03164 |
jPOSTi | Q03164 |
MassIVEi | Q03164 |
MaxQBi | Q03164 |
PaxDbi | Q03164 |
PeptideAtlasi | Q03164 |
PRIDEi | Q03164 |
ProteomicsDBi | 23014 58195 [Q03164-1] 58196 [Q03164-2] |
PTM databases
CarbonylDBi | Q03164 |
GlyConnecti | 2046, 1 N-Linked glycan (1 site) |
GlyGeni | Q03164, 17 sites, 2 N-linked glycans (1 site), 2 O-linked glycans (16 sites) |
iPTMneti | Q03164 |
PhosphoSitePlusi | Q03164 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000118058, Expressed in forebrain and 256 other tissues |
ExpressionAtlasi | Q03164, baseline and differential |
Genevisiblei | Q03164, HS |
Organism-specific databases
HPAi | ENSG00000118058, Low tissue specificity |
Interactioni
Subunit structurei
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 ARNTL/BMAL1 in a circadian manner (By similarity).
Interacts with PPIE; this results in decreased histone H3 methyltransferase activity (PubMed:20677832, PubMed:20541251).
Interacts with CREBBP (PubMed:16253272).
Interacts with the WRAD complex composed of WDR5, RBBP5, ASH2L and DPY30 (PubMed:22665483).
Interacts (via MBM motif) with MEN1 (PubMed:22936661, PubMed:22327296, PubMed:25305204).
Interacts (via IBM motifs) with PSIP1 (via IBD domain) with moderate affinity whereas the KMT2A-MEN1 complex interacts with a greater affinity; MEN1 enhances interaction of KMT2A with PSIP1 (PubMed:22327296, PubMed:25305204, PubMed:25082813, PubMed:29997176). Phosphorylation increases its affinity for PSIP1 (PubMed:29997176).
Forms a complex with CREBBP and CREB1 (PubMed:23651431).
By similarity25 PublicationsBinary interactionsi
Q03164
MLL cleavage product N320 (PRO_0000390949)
With | #Exp. | IntAct |
---|---|---|
PAX5 [Q02548] | 2 | EBI-2610266,EBI-296331 |
MLL cleavage product C180 (PRO_0000390950)
With | #Exp. | IntAct |
---|---|---|
KAT6A [Q92794] | 10 | EBI-2638616,EBI-948013 |
WDR5 [P61964] | 2 | EBI-2638616,EBI-540834 |
GO - Molecular functioni
- identical protein binding Source: IntAct
- lysine-acetylated histone binding Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 110443, 197 interactors |
ComplexPortali | CPX-5850, Histone-lysine N-methyltransferase complex, KMT2A variant |
CORUMi | Q03164 |
DIPi | DIP-29221N |
ELMi | Q03164 |
IntActi | Q03164, 64 interactors |
MINTi | Q03164 |
STRINGi | 9606.ENSP00000436786 |
Chemistry databases
BindingDBi | Q03164 |
Miscellaneous databases
RNActi | Q03164, protein |
Structurei
Secondary structure
3D structure databases
BMRBi | Q03164 |
SASBDBi | Q03164 |
SMRi | Q03164 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q03164 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1703 – 1748 | Bromo; divergentPROSITE-ProRule annotationAdd BLAST | 46 | |
Domaini | 2018 – 2074 | FYR N-terminalPROSITE-ProRule annotationAdd BLAST | 57 | |
Domaini | 3666 – 3747 | FYR C-terminalPROSITE-ProRule annotationAdd BLAST | 82 | |
Domaini | 3829 – 3945 | SETPROSITE-ProRule annotationAdd BLAST | 117 | |
Domaini | 3953 – 3969 | Post-SETPROSITE-ProRule annotationAdd BLAST | 17 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 108 | DisorderedSequence analysisAdd BLAST | 108 | |
Regioni | 132 – 253 | DisorderedSequence analysisAdd BLAST | 122 | |
Regioni | 301 – 352 | DisorderedSequence analysisAdd BLAST | 52 | |
Regioni | 445 – 585 | DisorderedSequence analysisAdd BLAST | 141 | |
Regioni | 713 – 780 | DisorderedSequence analysisAdd BLAST | 68 | |
Regioni | 798 – 949 | DisorderedSequence analysisAdd BLAST | 152 | |
Regioni | 1038 – 1066 | DisorderedSequence analysisAdd BLAST | 29 | |
Regioni | 1106 – 1166 | DisorderedSequence analysisAdd BLAST | 61 | |
Regioni | 1200 – 1375 | DisorderedSequence analysisAdd BLAST | 176 | |
Regioni | 1584 – 1600 | Interaction with histone H3K4me31 PublicationAdd BLAST | 17 | |
Regioni | 1663 – 1713 | DisorderedSequence analysisAdd BLAST | 51 | |
Regioni | 1806 – 1869 | DisorderedSequence analysisAdd BLAST | 64 | |
Regioni | 2081 – 2133 | DisorderedSequence analysisAdd BLAST | 53 | |
Regioni | 2145 – 2232 | DisorderedSequence analysisAdd BLAST | 88 | |
Regioni | 2275 – 2333 | DisorderedSequence analysisAdd BLAST | 59 | |
Regioni | 2373 – 2460 | DisorderedSequence analysisAdd BLAST | 88 | |
Regioni | 2475 – 2618 | DisorderedSequence analysisAdd BLAST | 144 | |
Regioni | 2647 – 2675 | DisorderedSequence analysisAdd BLAST | 29 | |
Regioni | 2713 – 2821 | DisorderedSequence analysisAdd BLAST | 109 | |
Regioni | 2961 – 3064 | DisorderedSequence analysisAdd BLAST | 104 | |
Regioni | 3166 – 3244 | DisorderedSequence analysisAdd BLAST | 79 | |
Regioni | 3464 – 3608 | DisorderedSequence analysisAdd BLAST | 145 | |
Regioni | 3620 – 3643 | DisorderedSequence analysisAdd BLAST | 24 | |
Regioni | 3785 – 3808 | DisorderedSequence analysisAdd BLAST | 24 | |
Regioni | 3906 – 3907 | S-adenosyl-L-methionine bindingCombined sources2 Publications | 2 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 6 – 25 | Menin-binding motif (MBM)1 PublicationAdd BLAST | 20 | |
Motifi | 123 – 134 | Integrase domain-binding motif 1 (IBM1)1 PublicationAdd BLAST | 12 | |
Motifi | 147 – 152 | Integrase domain-binding motif 2 (IBM2)1 Publication | 6 | |
Motifi | 2847 – 2855 | 9aaTAD1 Publication | 9 | |
Motifi | 3762 – 3767 | WDR5 interaction motif (WIN)2 Publications | 6 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 37 – 58 | Pro residuesSequence analysisAdd BLAST | 22 | |
Compositional biasi | 81 – 103 | Polar residuesSequence analysisAdd BLAST | 23 | |
Compositional biasi | 184 – 203 | Polar residuesSequence analysisAdd BLAST | 20 | |
Compositional biasi | 204 – 226 | Basic and acidic residuesSequence analysisAdd BLAST | 23 | |
Compositional biasi | 236 – 253 | Basic and acidic residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 325 – 351 | Basic and acidic residuesSequence analysisAdd BLAST | 27 | |
Compositional biasi | 445 – 495 | Polar residuesSequence analysisAdd BLAST | 51 | |
Compositional biasi | 535 – 556 | Polar residuesSequence analysisAdd BLAST | 22 | |
Compositional biasi | 557 – 576 | Pro residuesSequence analysisAdd BLAST | 20 | |
Compositional biasi | 713 – 731 | Polar residuesSequence analysisAdd BLAST | 19 | |
Compositional biasi | 747 – 780 | Polar residuesSequence analysisAdd BLAST | 34 | |
Compositional biasi | 798 – 845 | Polar residuesSequence analysisAdd BLAST | 48 | |
Compositional biasi | 846 – 898 | Basic and acidic residuesSequence analysisAdd BLAST | 53 | |
Compositional biasi | 1046 – 1061 | Polar residuesSequence analysisAdd BLAST | 16 | |
Compositional biasi | 1249 – 1272 | Basic and acidic residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 1278 – 1302 | Polar residuesSequence analysisAdd BLAST | 25 | |
Compositional biasi | 1303 – 1317 | Pro residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 1822 – 1847 | Pro residuesSequence analysisAdd BLAST | 26 | |
Compositional biasi | 2096 – 2118 | Polar residuesSequence analysisAdd BLAST | 23 | |
Compositional biasi | 2146 – 2174 | Polar residuesSequence analysisAdd BLAST | 29 | |
Compositional biasi | 2189 – 2232 | Polar residuesSequence analysisAdd BLAST | 44 | |
Compositional biasi | 2275 – 2320 | Polar residuesSequence analysisAdd BLAST | 46 | |
Compositional biasi | 2402 – 2418 | Polar residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 2419 – 2445 | Basic and acidic residuesSequence analysisAdd BLAST | 27 | |
Compositional biasi | 2526 – 2594 | Polar residuesSequence analysisAdd BLAST | 69 | |
Compositional biasi | 2721 – 2746 | Polar residuesSequence analysisAdd BLAST | 26 | |
Compositional biasi | 2747 – 2784 | Basic and acidic residuesSequence analysisAdd BLAST | 38 | |
Compositional biasi | 2785 – 2821 | Polar residuesSequence analysisAdd BLAST | 37 | |
Compositional biasi | 3011 – 3064 | Polar residuesSequence analysisAdd BLAST | 54 | |
Compositional biasi | 3166 – 3183 | Polar residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 3195 – 3222 | Polar residuesSequence analysisAdd BLAST | 28 | |
Compositional biasi | 3230 – 3244 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 3464 – 3530 | Polar residuesSequence analysisAdd BLAST | 67 | |
Compositional biasi | 3563 – 3606 | Polar residuesSequence analysisAdd BLAST | 44 |