| IED ID | IndEnz0002003600 |
| Enzyme Type ID | protease003600 |
| Protein Name |
Inactive histone-lysine N-methyltransferase 2E Inactive lysine N-methyltransferase 2E Myeloid/lymphoid or mixed-lineage leukemia protein 5 |
| Gene Name | KMT2E MLL5 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MSIVIPLGVDTAETSYLEMAAGSEPESVEASPVVVEKSNSYPHQLYTSSSHHSHSYIGLPYADHNYGARPPPTPPASPPPSVLISKNEVGIFTTPNFDETSSATTISTSEDGSYGTDVTRCICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIPDTYLCERCQPRNLDKERAVLLQRRKRENMSDGDTSATESGDEVPVELYTAFQHTPTSITLTASRVSKVNDKRRKKSGEKEQHISKCKKAFREGSRKSSRVKGSAPEIDPSSDGSNFGWETKIKAWMDRYEEANNNQYSEGVQREAQRIALRLGNGNDKKEMNKSDLNTNNLLFKPPVESHIQKNKKILKSAKDLPPDALIIEYRGKFMLREQFEANGYFFKRPYPFVLFYSKFHGLEMCVDARTFGNEARFIRRSCTPNAEVRHEIQDGTIHLYIYSIHSIPKGTEITIAFDFDYGNCKYKVDCACLKENPECPVLKRSSESMENINSGYETRRKKGKKDKDISKEKDTQNQNITLDCEGTTNKMKSPETKQRKLSPLRLSVSNNQEPDFIDDIEEKTPISNEVEMESEEQIAERKRKMTREERKMEAILQAFARLEKREKRREQALERISTAKTEVKTECKDTQIVSDAEVIQEQAKEENASKPTPAKVNRTKQRKSFSRSRTHIGQQRRRHRTVSMCSDIQPSSPDIEVTSQQNDIENTVLTIEPETETALAEIITETEVPALNKCPTKYPKTKKHLVNEWLSEKNEKTGKPSDGLSERPLRITTDPEVLATQLNSLPGLTYSPHVYSTPKHYIRFTSPFLSEKRRRKEPTENISGSCKKRWLKQALEEENSAILHRFNSPCQERSRSPAVNGENKSPLLLNDSCSLPDLTTPLKKRRFYQLLDSVYSETSTPTPSPYATPTHTDITPMDPSFATPPRIKSDDETCRNGYKPIYSPVTPVTPGTPGNTMHFENISSPESSPEIKRRTYSQEGYDRSSTMLTLGPFRNSNLTELGLQEIKTIGYTSPRSRTEVNRQCPGEKEPVSDLQLGLDAVEPTALHKTLETPAHDRAEPNSQLDSTHSGRGTMYSSWVKSPDRTGVNFSVNSNLRDLTPSHQLEVGGGFRISESKCLMQDDTRGMFMETTVFCTSEDGLVSGFGRTVNDNLIDGNCTPQNPPQKKKVSLLEYRKRQREARKSGSKTENFPLISVSPHASGSLSNNGDGCASSNDNGEQVDHTASLPLPTPATVYNATSEETSNNCPVKDATASEKNEPEVQWTASTSVEQVRERSYQRALLLSDHRKDKDSGGESPCVSCSPSHVQSSPSSHSNHIPQLQAKGPVPSFSELMEDPDPENPEPTTTNECPSPDTSQNTCKSPPKMSKPGSPGSVIPAQAHGKIFTKPDPQWDSTVSASEAENGVHLKTELQQKQLSNNNQALSKNHPPQTHVRNSSEQLSQKLPSVPTKLHCPPSPHLENPPKSSTPHTPVQHGYLSPKPPSQQLGSPYRPHHSQSPQVGTPQREPQRNFYPAAQNLPANTQQATSGTLFTQTPSGQSSATYSQFNQQSLNSTAPPPPPPPPPSSSYYQNQQPSANFQNYNQLKGSLSQQTVFTSGPNQALPGTTSQQTVPGHHVTPGHFLPSQNPTIHHQTAAAVVPPPPPPPPAPGPHLVQQPNSHQQHSVAHVVGPVHAVTPGSHIHSQTAGHHLPPPPPPPGPAPHHHPPPHPSTGLQGLQAQHQHVVNSAPPPPPPPPPSSVLASGHHTTSAQALHHPPHQGPPLFPSSAHPTVPPYPSQATHHTTLGPGPQHQPSGTGPHCPLPVTGPHLQPQGPNSIPTPTASGFCPHPGSVALPHGVQGPQQASPVPGQIPIHRAQVPPTFQNNYHGSGWH |
| Enzyme Length | 1858 |
| Uniprot Accession Number | Q8IZD2 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription (PubMed:23629655, PubMed:24130829, PubMed:23798402). Chromatin interaction is mediated via the binding to tri-methylated histone H3 at 'Lys-4' (H3K4me3) (PubMed:24130829, PubMed:23798402). Key regulator of hematopoiesis involved in terminal myeloid differentiation and in the regulation of hematopoietic stem cell (HSCs) self-renewal by a mechanism that involves DNA methylation (By similarity). Also acts as an important cell cycle regulator, participating in cell cycle regulatory network machinery at multiple cell cycle stages including G1/S transition, S phase progression and mitotic entry (PubMed:14718661, PubMed:18573682, PubMed:19264965, PubMed:23629655). Recruited to E2F1 responsive promoters by HCFC1 where it stimulates tri-methylation of histone H3 at 'Lys-4' and transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). During myoblast differentiation, required to suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells (By similarity). {ECO:0000250|UniProtKB:Q3UG20, ECO:0000269|PubMed:14718661, ECO:0000269|PubMed:18573682, ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829}.; FUNCTION: [Isoform NKp44L]: Cellular ligand for NCR2/NKp44, may play a role as a danger signal in cytotoxicity and NK-cell-mediated innate immunity. {ECO:0000269|PubMed:23958951}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (12); Beta strand (10); Chain (1); Coiled coil (1); Compositional bias (23); Domain (1); Glycosylation (2); Helix (4); Metal binding (8); Modified residue (6); Motif (1); Mutagenesis (6); Natural variant (13); Region (7); Sequence caution (4); Sequence conflict (12); Turn (3); Zinc finger (1) |
| Keywords | 3D-structure;Alternative splicing;Cell cycle;Cell membrane;Chromatin regulator;Chromosome;Coiled coil;Cytoplasm;Cytoskeleton;Disease variant;Glycoprotein;Growth arrest;Membrane;Mental retardation;Metal-binding;Nucleus;Phosphoprotein;Reference proteome;Transcription;Transcription regulation;Ubl conjugation;Zinc;Zinc-finger |
| Interact With | P04637; Q9HD20-3; O95944 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Chromosome {ECO:0000269|PubMed:23798402}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:23798402}. Nucleus speckle {ECO:0000269|PubMed:14718661}. Note=Absent from the nucleolus (PubMed:14718661). Localizes to chromosome during interphase and to centrosomes during mitosis (PubMed:23798402). Dissociation from mitotic chromosome is likely due to histone H3 phosphorylation on 'Thr-3' and 'Thr-6' (PubMed:23798402). {ECO:0000269|PubMed:14718661, ECO:0000269|PubMed:23798402}.; SUBCELLULAR LOCATION: [Isoform 3]: Nucleus, nucleoplasm {ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:26678539}. Nucleus speckle {ECO:0000269|PubMed:23798402}. Note=Absent from the nucleolus (PubMed:23629655). Localizes to chromosome during interphase and to nucleus speckle during mitosis (PubMed:23798402). Dissociation from mitotic chromosome is likely due to histone H3 phosphorylation on 'Thr-3' and 'Thr-6' (PubMed:23798402). {ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:23798402}.; SUBCELLULAR LOCATION: [Isoform NKp44L]: Cytoplasm {ECO:0000269|PubMed:23958951}. Cell membrane {ECO:0000269|PubMed:23958951}; Peripheral membrane protein {ECO:0000269|PubMed:23958951}. |
| Modified Residue | MOD_RES 623; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 837; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 845; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q3UG20; MOD_RES 1070; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 1273; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 1359; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163 |
| Post Translational Modification | PTM: Ubiquitinated. Deubiquitinated by USP7. {ECO:0000269|PubMed:26678539}.; PTM: O-glycosylated at Ser-435 and Thr-440 in the SET domain by OGT which probably prevents KMT2E proteasomal-mediated degradation. {ECO:0000269|PubMed:26678539}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (1); X-ray crystallography (2) |
| Cross Reference PDB | 2LV9; 4L58; 5HT6; |
| Mapped Pubmed ID | 12453418; 12483298; 12540855; 12576332; 12670868; 14992727; 15235609; 16199523; 16292313; 16628190; 16682010; 17021013; 17500065; 17707229; 18316480; 19114653; 19509293; 20195357; 20439461; 20711500; 21423215; 21832073; 22777353; 23414517; |
| Motif | MOTIF 63..66; /note=HCFC1-binding motif (HBM); /evidence=ECO:0000269|PubMed:23629655 |
| Gene Encoded By | |
| Mass | 204,965 |
| Kinetics | |
| Metal Binding | METAL 121; /note="Zinc 1"; /evidence="ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9, ECO:0007744|PDB:4L58"; METAL 123; /note="Zinc 1"; /evidence="ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9, ECO:0007744|PDB:4L58"; METAL 135; /note="Zinc 2"; /evidence="ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9, ECO:0007744|PDB:4L58"; METAL 138; /note="Zinc 2"; /evidence="ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9, ECO:0007744|PDB:4L58"; METAL 143; /note="Zinc 1; via pros nitrogen"; /evidence="ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9, ECO:0007744|PDB:4L58"; METAL 146; /note="Zinc 1"; /evidence="ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9, ECO:0007744|PDB:4L58"; METAL 160; /note="Zinc 2"; /evidence="ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9, ECO:0007744|PDB:4L58"; METAL 163; /note="Zinc 2"; /evidence="ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829, ECO:0007744|PDB:2LV9, ECO:0007744|PDB:4L58" |
| Rhea ID | |
| Cross Reference Brenda |