DOT1L_HUMAN
ID DOT1L_HUMAN Reviewed; 1537 AA.
AC Q8TEK3; O60379; Q96JL1;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 3.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-79 specific {ECO:0000305};
DE EC=2.1.1.360 {ECO:0000269|PubMed:12123582};
DE AltName: Full=DOT1-like protein;
DE AltName: Full=Histone H3-K79 methyltransferase;
DE Short=H3-K79-HMTase;
DE AltName: Full=Lysine N-methyltransferase 4;
GN Name=DOT1L {ECO:0000312|HGNC:HGNC:24948}; Synonyms=KIAA1814, KMT4;
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), CATALYTIC ACTIVITY, MUTAGENESIS OF
RP 163-GLY--GLY-165, AND FUNCTION.
RX PubMed=12123582; DOI=10.1016/s0960-9822(02)00901-6;
RA Feng Q., Wang H., Ng H.H., Erdjument-Bromage H., Tempst P., Struhl K.,
RA Zhang Y.;
RT "Methylation of H3-lysine 79 is mediated by a new family of HMTases without
RT a SET domain.";
RL Curr. Biol. 12:1052-1058(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 454-1537 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [4]
RP PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Spleen;
RX PubMed=12693554; DOI=10.1093/dnares/10.1.49;
RA Jikuya H., Takano J., Kikuno R., Hirosawa M., Nagase T., Nomura N.,
RA Ohara O.;
RT "Characterization of long cDNA clones from human adult spleen. II. The
RT complete sequences of 81 cDNA clones.";
RL DNA Res. 10:49-57(2003).
RN [5]
RP INTERACTION WITH MLLT10, AND SUBCELLULAR LOCATION.
RX PubMed=15851025; DOI=10.1016/j.cell.2005.02.020;
RA Okada Y., Feng Q., Lin Y., Jiang Q., Li Y., Coffield V.M., Su L., Xu G.,
RA Zhang Y.;
RT "hDOT1L links histone methylation to leukemogenesis.";
RL Cell 121:167-178(2005).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1001, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-374; SER-775; SER-1001 AND
RP SER-1009, AND IDENTIFICATION BY 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 [8]
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-374; THR-900; SER-902 AND
RP SER-1001, 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-374; SER-471; THR-480;
RP SER-775; SER-834; SER-902; SER-1001; SER-1035 AND SER-1213, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-374 AND SER-902, AND
RP IDENTIFICATION BY 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-297; SER-374; SER-448;
RP SER-775; SER-786; SER-826; SER-834; THR-900; SER-902; THR-984; SER-997;
RP SER-1001; SER-1009; SER-1035; SER-1093; SER-1104; SER-1213 AND SER-1246,
RP AND 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 [13]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-416 IN COMPLEX WITH
RP S-ADENOSINE-L-METHIONINE, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS
RP OF ASN-241 AND TYR-312, NUCLEOSOME BINDING, AND INTERACTION WITH DNA.
RX PubMed=12628190; DOI=10.1016/s0092-8674(03)00114-4;
RA Min J., Feng Q., Li Z., Zhang Y., Xu R.-M.;
RT "Structure of the catalytic domain of human DOT1L, a non-SET domain
RT nucleosomal histone methyltransferase.";
RL Cell 112:711-723(2003).
CC -!- FUNCTION: Histone methyltransferase. Methylates 'Lys-79' of histone H3.
CC Nucleosomes are preferred as substrate compared to free histones
CC (PubMed:12123582). Binds to DNA (PubMed:12628190).
CC {ECO:0000269|PubMed:12123582, ECO:0000269|PubMed:12628190}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(79)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+)
CC + N(6),N(6),N(6)-trimethyl-L-lysyl(79)-[histone H3] + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60328, Rhea:RHEA-COMP:15549, Rhea:RHEA-
CC COMP:15552, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.360;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00902,
CC ECO:0000269|PubMed:12123582};
CC -!- SUBUNIT: Interacts with MLLT10. {ECO:0000269|PubMed:12628190,
CC ECO:0000269|PubMed:15851025}.
CC -!- INTERACTION:
CC Q8TEK3; Q03111: MLLT1; NbExp=6; IntAct=EBI-2619253, EBI-1384215;
CC Q8TEK3; P42568: MLLT3; NbExp=6; IntAct=EBI-2619253, EBI-716132;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15851025}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TEK3-2; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TEK3-1; Sequence=VSP_059795;
CC -!- MISCELLANEOUS: In contrast to other lysine histone methyltransferases,
CC it does not contain a SET domain, suggesting the existence of another
CC mechanism for methylation of lysine residues of histones.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. DOT1 family. {ECO:0000255|PROSITE-ProRule:PRU00902}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC08316.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF509504; AAM88322.1; -; mRNA.
DR EMBL; AC004490; AAC08316.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB058717; BAB47443.1; -; mRNA.
DR EMBL; AK074120; BAB84946.1; -; mRNA.
DR CCDS; CCDS42460.1; -. [Q8TEK3-2]
DR RefSeq; NP_115871.1; NM_032482.2. [Q8TEK3-2]
DR PDB; 1NW3; X-ray; 2.50 A; A=1-416.
DR PDB; 2MV7; NMR; -; B=877-900.
DR PDB; 3QOW; X-ray; 2.10 A; A=1-416.
DR PDB; 3QOX; X-ray; 2.30 A; A=1-416.
DR PDB; 3SR4; X-ray; 2.50 A; A=1-351.
DR PDB; 3SX0; X-ray; 2.28 A; A=1-420.
DR PDB; 3UWP; X-ray; 2.05 A; A=1-420.
DR PDB; 4EK9; X-ray; 2.50 A; A=1-416.
DR PDB; 4EKG; X-ray; 2.80 A; A=1-416.
DR PDB; 4EKI; X-ray; 2.85 A; A=1-416.
DR PDB; 4EQZ; X-ray; 2.15 A; A=1-420.
DR PDB; 4ER0; X-ray; 2.50 A; A=1-420.
DR PDB; 4ER3; X-ray; 2.40 A; A=1-351.
DR PDB; 4ER5; X-ray; 2.57 A; A=1-412.
DR PDB; 4ER6; X-ray; 2.30 A; A=1-412.
DR PDB; 4ER7; X-ray; 2.20 A; A=1-420.
DR PDB; 4HRA; X-ray; 3.15 A; A=1-416.
DR PDB; 4WVL; X-ray; 2.41 A; A=1-347.
DR PDB; 5DRT; X-ray; 2.69 A; A/B=2-333.
DR PDB; 5DRY; X-ray; 2.41 A; A/B=2-333.
DR PDB; 5DSX; X-ray; 2.41 A; A/B=2-332.
DR PDB; 5DT2; X-ray; 2.30 A; A/B=2-332.
DR PDB; 5DTM; X-ray; 2.20 A; A/B=2-332.
DR PDB; 5DTQ; X-ray; 2.61 A; A/B=2-332.
DR PDB; 5DTR; X-ray; 2.34 A; A/B=2-332.
DR PDB; 5JUW; X-ray; 2.28 A; A=1-420.
DR PDB; 5MVS; X-ray; 2.18 A; A/B=2-332.
DR PDB; 5MW3; X-ray; 2.09 A; A/B=2-332.
DR PDB; 5MW4; X-ray; 2.19 A; A/B=2-332.
DR PDB; 6IN3; X-ray; 2.30 A; A=4-330.
DR PDB; 6J99; EM; 4.10 A; K=1-416.
DR PDB; 6JM9; EM; 7.30 A; X=5-332.
DR PDB; 6JMA; EM; 6.80 A; X=5-332.
DR PDB; 6JN2; X-ray; 3.60 A; B=470-550.
DR PDB; 6NJ9; EM; 2.96 A; K=2-416.
DR PDB; 6NN6; EM; 3.90 A; K=3-416.
DR PDB; 6NOG; EM; 3.90 A; K=2-416.
DR PDB; 6NQA; EM; 3.54 A; K=2-416.
DR PDB; 6O96; EM; 3.50 A; K=2-332.
DR PDB; 6TE6; X-ray; 1.98 A; A/B=2-332.
DR PDB; 6TEL; X-ray; 2.19 A; A/B=2-332.
DR PDB; 6TEN; X-ray; 2.21 A; A/B=2-332.
DR PDB; 7BWD; EM; 4.32 A; K=1-416.
DR PDB; 7EDP; X-ray; 2.20 A; B=610-649.
DR PDBsum; 1NW3; -.
DR PDBsum; 2MV7; -.
DR PDBsum; 3QOW; -.
DR PDBsum; 3QOX; -.
DR PDBsum; 3SR4; -.
DR PDBsum; 3SX0; -.
DR PDBsum; 3UWP; -.
DR PDBsum; 4EK9; -.
DR PDBsum; 4EKG; -.
DR PDBsum; 4EKI; -.
DR PDBsum; 4EQZ; -.
DR PDBsum; 4ER0; -.
DR PDBsum; 4ER3; -.
DR PDBsum; 4ER5; -.
DR PDBsum; 4ER6; -.
DR PDBsum; 4ER7; -.
DR PDBsum; 4HRA; -.
DR PDBsum; 4WVL; -.
DR PDBsum; 5DRT; -.
DR PDBsum; 5DRY; -.
DR PDBsum; 5DSX; -.
DR PDBsum; 5DT2; -.
DR PDBsum; 5DTM; -.
DR PDBsum; 5DTQ; -.
DR PDBsum; 5DTR; -.
DR PDBsum; 5JUW; -.
DR PDBsum; 5MVS; -.
DR PDBsum; 5MW3; -.
DR PDBsum; 5MW4; -.
DR PDBsum; 6IN3; -.
DR PDBsum; 6J99; -.
DR PDBsum; 6JM9; -.
DR PDBsum; 6JMA; -.
DR PDBsum; 6JN2; -.
DR PDBsum; 6NJ9; -.
DR PDBsum; 6NN6; -.
DR PDBsum; 6NOG; -.
DR PDBsum; 6NQA; -.
DR PDBsum; 6O96; -.
DR PDBsum; 6TE6; -.
DR PDBsum; 6TEL; -.
DR PDBsum; 6TEN; -.
DR PDBsum; 7BWD; -.
DR PDBsum; 7EDP; -.
DR AlphaFoldDB; Q8TEK3; -.
DR SMR; Q8TEK3; -.
DR BioGRID; 124082; 77.
DR DIP; DIP-56410N; -.
DR IntAct; Q8TEK3; 32.
DR MINT; Q8TEK3; -.
DR STRING; 9606.ENSP00000381657; -.
DR BindingDB; Q8TEK3; -.
DR ChEMBL; CHEMBL1795117; -.
DR GuidetoPHARMACOLOGY; 2650; -.
DR GlyGen; Q8TEK3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8TEK3; -.
DR PhosphoSitePlus; Q8TEK3; -.
DR BioMuta; DOT1L; -.
DR DMDM; 25090171; -.
DR EPD; Q8TEK3; -.
DR jPOST; Q8TEK3; -.
DR MassIVE; Q8TEK3; -.
DR MaxQB; Q8TEK3; -.
DR PaxDb; Q8TEK3; -.
DR PeptideAtlas; Q8TEK3; -.
DR PRIDE; Q8TEK3; -.
DR ProteomicsDB; 74468; -. [Q8TEK3-1]
DR ProteomicsDB; 74469; -. [Q8TEK3-2]
DR ABCD; Q8TEK3; 1 sequenced antibody.
DR Antibodypedia; 22937; 538 antibodies from 32 providers.
DR DNASU; 84444; -.
DR Ensembl; ENST00000398665.8; ENSP00000381657.3; ENSG00000104885.19. [Q8TEK3-2]
DR GeneID; 84444; -.
DR KEGG; hsa:84444; -.
DR MANE-Select; ENST00000398665.8; ENSP00000381657.3; NM_032482.3; NP_115871.1.
DR UCSC; uc002lvb.4; human. [Q8TEK3-2]
DR CTD; 84444; -.
DR DisGeNET; 84444; -.
DR GeneCards; DOT1L; -.
DR HGNC; HGNC:24948; DOT1L.
DR HPA; ENSG00000104885; Tissue enriched (testis).
DR MIM; 607375; gene.
DR neXtProt; NX_Q8TEK3; -.
DR OpenTargets; ENSG00000104885; -.
DR PharmGKB; PA134993717; -.
DR VEuPathDB; HostDB:ENSG00000104885; -.
DR eggNOG; KOG3924; Eukaryota.
DR GeneTree; ENSGT00390000013515; -.
DR HOGENOM; CLU_004082_1_0_1; -.
DR InParanoid; Q8TEK3; -.
DR OMA; SEKQRRC; -.
DR OrthoDB; 88676at2759; -.
DR PhylomeDB; Q8TEK3; -.
DR TreeFam; TF106393; -.
DR BioCyc; MetaCyc:HS02643-MON; -.
DR BRENDA; 2.1.1.355; 2681.
DR BRENDA; 2.1.1.360; 2681.
DR PathwayCommons; Q8TEK3; -.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR SignaLink; Q8TEK3; -.
DR SIGNOR; Q8TEK3; -.
DR BioGRID-ORCS; 84444; 94 hits in 1098 CRISPR screens.
DR ChiTaRS; DOT1L; human.
DR EvolutionaryTrace; Q8TEK3; -.
DR GeneWiki; DOT1L; -.
DR GenomeRNAi; 84444; -.
DR Pharos; Q8TEK3; Tchem.
DR PRO; PR:Q8TEK3; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8TEK3; protein.
DR Bgee; ENSG00000104885; Expressed in right testis and 122 other tissues.
DR ExpressionAtlas; Q8TEK3; baseline and differential.
DR Genevisible; Q8TEK3; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042054; F:histone methyltransferase activity; IDA:MGI.
DR GO; GO:0031151; F:histone methyltransferase activity (H3-K79 specific); IBA:GO_Central.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IMP:UniProtKB.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:0006281; P:DNA repair; IBA:GO_Central.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0031507; P:heterochromatin assembly; IEA:InterPro.
DR GO; GO:0034729; P:histone H3-K79 methylation; IDA:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; IDA:UniProtKB.
DR GO; GO:2000677; P:regulation of transcription regulatory region DNA binding; IMP:UniProtKB.
DR GO; GO:0032200; P:telomere organization; TAS:BHF-UCL.
DR DisProt; DP01985; -.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR025789; DOT1_dom.
DR InterPro; IPR021169; DOT1L/grappa.
DR InterPro; IPR030445; H3-K79_meTrfase.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR21451; PTHR21451; 2.
DR Pfam; PF08123; DOT1; 1.
DR PIRSF; PIRSF037123; Histone_H3-K79_MeTrfase_met; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51569; DOT1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator; DNA-binding;
KW Methyltransferase; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..1537
FT /note="Histone-lysine N-methyltransferase, H3 lysine-79
FT specific"
FT /id="PRO_0000186089"
FT DOMAIN 16..330
FT /note="DOT1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT REGION 334..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 391..416
FT /note="Required for interaction with nucleosomes and DNA"
FT /evidence="ECO:0000269|PubMed:12628190"
FT REGION 785..853
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 893..912
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 957..1128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1145..1243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1334..1410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 334..349
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 390..415
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 416..431
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 433..467
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 809..823
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 962..991
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 998..1012
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1051..1068
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 136..139
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 159..168
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 186
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 222..223
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT MOD_RES 297
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 448
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 480
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 775
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 786
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 826
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 834
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 900
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 902
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 984
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 997
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1001
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1009
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1035
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1093
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1104
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1213
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1246
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1537
FT /note="N -> VVFNHAVPSASAHPFGARVGRGAACGSATLGPSPLQAAASASASSFQ
FT APASVETRPPPPPPPPPPPLPPPAHLGRSPAGPPVLHAPPPPNAALPPPPTLLASNPEP
FT ALLQSLASLPPNQAFLPPTSAASLPPANASLSIKLTSLPHKGARPSFTVHHQPLPRLAL
FT AQAAPGIPQASATGPSAVWVSLGMPPPYAAHLSGVKPR (in isoform 2)"
FT /id="VSP_059795"
FT VARIANT 726
FT /note="L -> M (in dbSNP:rs880525)"
FT /id="VAR_014287"
FT VARIANT 1386
FT /note="G -> S (in dbSNP:rs3815308)"
FT /id="VAR_014288"
FT VARIANT 1418
FT /note="V -> L (in dbSNP:rs2302061)"
FT /id="VAR_014289"
FT MUTAGEN 163..165
FT /note="GSG->RCR: Abolishes methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:12123582"
FT MUTAGEN 241
FT /note="N->A,D: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12628190"
FT MUTAGEN 312
FT /note="Y->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12628190"
FT MUTAGEN 312
FT /note="Y->F: No effect."
FT /evidence="ECO:0000269|PubMed:12628190"
FT CONFLICT 210
FT /note="G -> E (in Ref. 4; BAB84946)"
FT /evidence="ECO:0000305"
FT CONFLICT 454..467
FT /note="RSPHSPFYQLPPSV -> TLRTPSGSPRRTKL (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 464
FT /note="P -> L (in Ref. 4; BAB84946)"
FT /evidence="ECO:0000305"
FT STRAND 6..9
FT /evidence="ECO:0007829|PDB:6TE6"
FT STRAND 12..14
FT /evidence="ECO:0007829|PDB:6NJ9"
FT STRAND 18..23
FT /evidence="ECO:0007829|PDB:6TE6"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:6TE6"
FT HELIX 33..47
FT /evidence="ECO:0007829|PDB:6TE6"
FT HELIX 49..54
FT /evidence="ECO:0007829|PDB:6TE6"
FT HELIX 57..60
FT /evidence="ECO:0007829|PDB:6TE6"
FT HELIX 68..90
FT /evidence="ECO:0007829|PDB:6TE6"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:3UWP"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:4ER7"
FT HELIX 104..118
FT /evidence="ECO:0007829|PDB:6TE6"
FT HELIX 122..125
FT /evidence="ECO:0007829|PDB:6TE6"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:4EQZ"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:6TE6"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:6TE6"
FT TURN 136..139
FT /evidence="ECO:0007829|PDB:6TE6"
FT HELIX 140..151
FT /evidence="ECO:0007829|PDB:6TE6"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:6O96"
FT STRAND 158..163
FT /evidence="ECO:0007829|PDB:6TE6"
FT HELIX 168..176
FT /evidence="ECO:0007829|PDB:6TE6"
FT STRAND 180..186
FT /evidence="ECO:0007829|PDB:6TE6"
FT HELIX 189..209
FT /evidence="ECO:0007829|PDB:6TE6"
FT STRAND 216..220
FT /evidence="ECO:0007829|PDB:6TE6"
FT HELIX 226..233
FT /evidence="ECO:0007829|PDB:6TE6"
FT STRAND 236..240
FT /evidence="ECO:0007829|PDB:6TE6"
FT TURN 243..245
FT /evidence="ECO:0007829|PDB:3QOW"
FT HELIX 247..257
FT /evidence="ECO:0007829|PDB:6TE6"
FT STRAND 265..270
FT /evidence="ECO:0007829|PDB:6TE6"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:3UWP"
FT HELIX 287..289
FT /evidence="ECO:0007829|PDB:6TE6"
FT STRAND 290..296
FT /evidence="ECO:0007829|PDB:6TE6"
FT TURN 298..300
FT /evidence="ECO:0007829|PDB:5DTM"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:5MW4"
FT STRAND 307..309
FT /evidence="ECO:0007829|PDB:4ER7"
FT STRAND 312..317
FT /evidence="ECO:0007829|PDB:6TE6"
FT HELIX 320..330
FT /evidence="ECO:0007829|PDB:6TE6"
FT HELIX 332..342
FT /evidence="ECO:0007829|PDB:3UWP"
FT HELIX 611..648
FT /evidence="ECO:0007829|PDB:7EDP"
FT STRAND 880..882
FT /evidence="ECO:0007829|PDB:2MV7"
FT TURN 885..887
FT /evidence="ECO:0007829|PDB:2MV7"
SQ SEQUENCE 1537 AA; 164856 MW; 9CEA12850DC4ACB1 CRC64;
MGEKLELRLK SPVGAEPAVY PWPLPVYDKH HDAAHEIIET IRWVCEEIPD LKLAMENYVL
IDYDTKSFES MQRLCDKYNR AIDSIHQLWK GTTQPMKLNT RPSTGLLRHI LQQVYNHSVT
DPEKLNNYEP FSPEVYGETS FDLVAQMIDE IKMTDDDLFV DLGSGVGQVV LQVAAATNCK
HHYGVEKADI PAKYAETMDR EFRKWMKWYG KKHAEYTLER GDFLSEEWRE RIANTSVIFV
NNFAFGPEVD HQLKERFANM KEGGRIVSSK PFAPLNFRIN SRNLSDIGTI MRVVELSPLK
GSVSWTGKPV SYYLHTIDRT ILENYFSSLK NPKLREEQEA ARRRQQRESK SNAATPTKGP
EGKVAGPADA PMDSGAEEEK AGAATVKKPS PSKARKKKLN KKGRKMAGRK RGRPKKMNTA
NPERKPKKNQ TALDALHAQT VSQTAASSPQ DAYRSPHSPF YQLPPSVQRH SPNPLLVAPT
PPALQKLLES FKIQYLQFLA YTKTPQYKAS LQELLGQEKE KNAQLLGAAQ QLLSHCQAQK
EEIRRLFQQK LDELGVKALT YNDLIQAQKE ISAHNQQLRE QSEQLEQDNR ALRGQSLQLL
KARCEELQLD WATLSLEKLL KEKQALKSQI SEKQRHCLEL QISIVELEKS QRQQELLQLK
SCVPPDDALS LHLRGKGALG RELEPDASRL HLELDCTKFS LPHLSSMSPE LSMNGQAAGY
ELCGVLSRPS SKQNTPQYLA SPLDQEVVPC TPSHVGRPRL EKLSGLAAPD YTRLSPAKIV
LRRHLSQDHT VPGRPAASEL HSRAEHTKEN GLPYQSPSVP GSMKLSPQDP RPLSPGALQL
AGEKSSEKGL RERAYGSSGE LITSLPISIP LSTVQPNKLP VSIPLASVVL PSRAERARST
PSPVLQPRDP SSTLEKQIGA NAHGAGSRSL ALAPAGFSYA GSVAISGALA GSPASLTPGA
EPATLDESSS SGSLFATVGS RSSTPQHPLL LAQPRNSLPA SPAHQLSSSP RLGGAAQGPL
PEASKGDLPS DSGFSDPESE AKRRIVFTIT TGAGSAKQSP SSKHSPLTAS ARGDCVPSHG
QDSRRRGRRK RASAGTPSLS AGVSPKRRAL PSVAGLFTQP SGSPLNLNSM VSNINQPLEI
TAISSPETSL KSSPVPYQDH DQPPVLKKER PLSQTNGAHY SPLTSDEEPG SEDEPSSARI
ERKIATISLE SKSPPKTLEN GGGLAGRKPA PAGEPVNSSK WKSTFSPISD IGLAKSADSP
LQASSALSQN SLFTFRPALE EPSADAKLAA HPRKGFPGSL SGADGLSPGT NPANGCTFGG
GLAADLSLHS FSDGASLPHK GPEAAGLSSP LSFPSQRGKE GSDANPFLSK RQLDGLAGLK
GEGSRGKEAG EGGLPLCGPT DKTPLLSGKA AKARDREVDL KNGHNLFISA AAVPPGSLLS
GPGLAPAASS AGGAASSAQT HRSFLGPFPP GPQFALGPMS LQANLGSVAG SSVLQSLFSS
VPAAAGLVHV SSAATRLTNS HAMGSFSGVA GGTVGGN
