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NameHistone-lysine N-methyltransferase, H3 lysine-79 specific
Synonyms
  • 2.1.1.43
  • DOT1-like protein
  • H3-K79-HMTase
  • Histone H3-K79 methyltransferase
  • KIAA1814
  • KMT4
  • Lysine N-methyltransferase 4
Gene NameDOT1L
OrganismHuman
Amino acid sequence
>lcl|BSEQ0006302|Histone-lysine N-methyltransferase, H3 lysine-79 specific
MGEKLELRLKSPVGAEPAVYPWPLPVYDKHHDAAHEIIETIRWVCEEIPDLKLAMENYVL
IDYDTKSFESMQRLCDKYNRAIDSIHQLWKGTTQPMKLNTRPSTGLLRHILQQVYNHSVT
DPEKLNNYEPFSPEVYGETSFDLVAQMIDEIKMTDDDLFVDLGSGVGQVVLQVAAATNCK
HHYGVEKADIPAKYAETMDREFRKWMKWYGKKHAEYTLERGDFLSEEWRERIANTSVIFV
NNFAFGPEVDHQLKERFANMKEGGRIVSSKPFAPLNFRINSRNLSDIGTIMRVVELSPLK
GSVSWTGKPVSYYLHTIDRTILENYFSSLKNPKLREEQEAARRRQQRESKSNAATPTKGP
EGKVAGPADAPMDSGAEEEKAGAATVKKPSPSKARKKKLNKKGRKMAGRKRGRPKKMNTA
NPERKPKKNQTALDALHAQTVSQTAASSPQDAYRSPHSPFYQLPPSVQRHSPNPLLVAPT
PPALQKLLESFKIQYLQFLAYTKTPQYKASLQELLGQEKEKNAQLLGAAQQLLSHCQAQK
EEIRRLFQQKLDELGVKALTYNDLIQAQKEISAHNQQLREQSEQLEQDNRALRGQSLQLL
KARCEELQLDWATLSLEKLLKEKQALKSQISEKQRHCLELQISIVELEKSQRQQELLQLK
SCVPPDDALSLHLRGKGALGRELEPDASRLHLELDCTKFSLPHLSSMSPELSMNGQAAGY
ELCGVLSRPSSKQNTPQYLASPLDQEVVPCTPSHVGRPRLEKLSGLAAPDYTRLSPAKIV
LRRHLSQDHTVPGRPAASELHSRAEHTKENGLPYQSPSVPGSMKLSPQDPRPLSPGALQL
AGEKSSEKGLRERAYGSSGELITSLPISIPLSTVQPNKLPVSIPLASVVLPSRAERARST
PSPVLQPRDPSSTLEKQIGANAHGAGSRSLALAPAGFSYAGSVAISGALAGSPASLTPGA
EPATLDESSSSGSLFATVGSRSSTPQHPLLLAQPRNSLPASPAHQLSSSPRLGGAAQGPL
PEASKGDLPSDSGFSDPESEAKRRIVFTITTGAGSAKQSPSSKHSPLTASARGDCVPSHG
QDSRRRGRRKRASAGTPSLSAGVSPKRRALPSVAGLFTQPSGSPLNLNSMVSNINQPLEI
TAISSPETSLKSSPVPYQDHDQPPVLKKERPLSQTNGAHYSPLTSDEEPGSEDEPSSARI
ERKIATISLESKSPPKTLENGGGLAGRKPAPAGEPVNSSKWKSTFSPISDIGLAKSADSP
LQASSALSQNSLFTFRPALEEPSADAKLAAHPRKGFPGSLSGADGLSPGTNPANGCTFGG
GLAADLSLHSFSDGASLPHKGPEAAGLSSPLSFPSQRGKEGSDANPFLSKRQLDGLAGLK
GEGSRGKEAGEGGLPLCGPTDKTPLLSGKAAKARDREVDLKNGHNLFISAAAVPPGSLLS
GPGLAPAASSAGGAASSAQTHRSFLGPFPPGPQFALGPMSLQANLGSVAGSSVLQSLFSS
VPAAAGLVHVSSAATRLTNSHAMGSFSGVAGGTVGGVVFNHAVPSASAHPFGARVGRGAA
CGSATLGPSPLQAAASASASSFQAPASVETRPPPPPPPPPPPLPPPAHLGRSPAGPPVLH
APPPPNAALPPPPTLLASNPEPALLQSLASLPPNQAFLPPTSAASLPPANASLSIKLTSL
PHKGARPSFTVHHQPLPRLALAQAAPGIPQASATGPSAVWVSLGMPPPYAAHLSGVKPR
Number of residues1739
Molecular Weight184851.18
Theoretical pI9.88
GO Classification
Functions
  • DNA binding
  • transcription factor binding
  • histone-lysine N-methyltransferase activity
  • histone methyltransferase activity (H3-K79 specific)
Processes
  • regulation of JAK-STAT cascade
  • regulation of transcription regulatory region DNA binding
  • regulation of cell cycle
  • chromatin silencing
  • chromatin organization
Components
  • nucleoplasm
General FunctionTranscription factor binding
Specific FunctionHistone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ8TEK3
UniProtKB Entry NameDOT1L_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0019387|Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L)
ATGGGGGAGAAGCTGGAGCTGAGACTGAAGTCGCCCGTGGGGGCTGAGCCCGCCGTCTAC
CCGTGGCCGCTGCCGGTCTACGATAAACATCACGATGCTGCTCATGAAATCATCGAGACC
ATCCGATGGGTCTGTGAAGAAATCCCGGATCTCAAGCTCGCTATGGAGAATTACGTTTTA
ATTGACTATGACACCAAAAGCTTCGAGAGCATGCAGAGGCTCTGCGACAAGTACAACCGT
GCCATCGACAGCATCCACCAGCTGTGGAAGGGCACCACGCAGCCCATGAAGCTGAACACG
CGGCCGTCCACTGGACTCCTGCGCCATATCCTGCAGCAGGTCTACAACCACTCGGTGACC
GACCCCGAGAAGCTCAACAACTACGAGCCCTTCTCCCCCGAGGTGTACGGGGAGACCTCC
TTCGACCTGGTGGCCCAGATGATTGATGAGATCAAGATGACCGACGACGACCTGTTTGTG
GACTTGGGGAGCGGTGTGGGCCAGGTCGTGCTCCAGGTTGCTGCTGCCACCAACTGCAAA
CATCACTATGGCGTCGAGAAAGCAGACATCCCGGCCAAGTATGCGGAGACCATGGACCGC
GAGTTCAGGAAGTGGATGAAATGGTATGGAAAAAAGCATGCAGAATACACATTGGAGAGA
GGCGATTTCCTCTCAGAAGAGTGGAGGGAGCGAATCGCCAACACGAGTGTTATATTTGTG
AATAATTTTGCCTTTGGTCCTGAGGTGGATCACCAGCTGAAGGAGCGGTTTGCAAACATG
AAGGAAGGTGGCAGAATCGTGTCCTCGAAACCCTTTGCACCTCTGAACTTCAGAATAAAC
AGTAGAAACTTGAGTGACATCGGCACCATCATGCGCGTGGTGGAGCTCTCGCCCCTGAAG
GGCTCGGTGTCGTGGACGGGGAAGCCAGTCTCCTACTACCTGCACACTATCGACCGCACC
ATACTTGAAAACTATTTTTCTAGTCTGAAAAACCCAAAACTCAGGGAGGAACAGGAGGCA
GCCCGGCGCCGCCAGCAGCGCGAGAGCAAGAGCAACGCGGCCACGCCCACTAAGGGCCCA
GAGGGCAAGGTGGCCGGCCCCGCCGACGCCCCCATGGACTCTGGTGCTGAGGAAGAGAAG
GCGGGAGCAGCCACCGTGAAGAAGCCGTCTCCCTCCAAAGCCCGCAAGAAGAAGCTAAAC
AAGAAGGGGAGGAAGATGGCTGGCCGCAAGCGCGGGCGCCCCAAGAAGATGAACACTGCG
AACCCCGAGCGGAAGCCCAAGAAGAACCAAACTGCACTGGATGCCCTGCACGCTCAGACC
GTGTCTCAGACGGCGGCCTCCTCACCCCAGGATGCCTACAGATCCCCTCACAGCCCGTTC
TACCAGCTACCTCCGAGCGTGCAGCGGCACTCCCCCAACCCGCTGCTGGTGGCGCCCACC
CCGCCCGCGCTGCAGAAGCTTCTAGAGTCCTTCAAGATCCAGTACCTGCAGTTCCTGGCA
TACACAAAGACCCCCCAGTACAAGGCCAGCCTGCAGGAGCTGCTGGGCCAGGAGAAGGAG
AAGAACGCCCAGCTCCTGGGTGCGGCTCAGCAGCTCCTCAGCCACTGCCAGGCCCAGAAG
GAGGAGATCAGGAGGCTGTTTCAGCAAAAATTGGATGAGCTGGGTGTGAAGGCGCTGACC
TACAACGACCTGATTCAAGCGCAGAAGGAGATCTCCGCCCATAACCAGCAGCTGCGGGAG
CAGTCGGAGCAGCTGGAGCAGGACAACCGCGCGCTCCGCGGCCAGAGCTTGCAGCTGCTC
AAGGCTCGCTGCGAGGAGCTGCAGCTGGACTGGGCCACGCTGTCGCTGGAGAAGCTGTTG
AAGGAGAAGCAGGCCCTGAAGAGCCAGATCTCGGAGAAGCAGAGGCACTGCCTGGAGCTG
CAGATCAGCATTGTGGAGCTAGAGAAGAGCCAGCGGCAGCAGGAGCTCCTGCAGCTCAAG
TCCTGTGTGCCGCCTGACGACGCCCTGTCCCTGCACCTGCGTGGGAAGGGCGCCCTGGGC
CGCGAGCTGGAGCCTGACGCCAGCCGGCTGCACCTGGAGCTGGACTGCACCAAGTTCTCG
CTGCCTCACTTGAGCAGCATGAGCCCGGAGCTCTCCATGAACGGCCAGGCTGCTGGCTAT
GAGCTCTGCGGTGTGCTGAGCCGGCCTTCGTCGAAGCAGAACACGCCCCAGTACCTGGCC
TCACCCCTGGACCAGGAGGTGGTGCCCTGTACCCCTAGCCACGTCGGCCGGCCGCGCCTG
GAGAAGCTGTCTGGCCTAGCCGCACCCGACTACACTAGGCTGTCCCCGGCCAAGATTGTG
CTGAGGCGGCACCTGAGCCAGGACCACACGGTGCCCGGCAGGCCGGCTGCCAGTGAGCTG
CATTCGAGAGCTGAGCACACCAAGGAGAACGGCCTTCCCTACCAGAGCCCCAGCGTGCCT
GGCAGCATGAAGCTGAGCCCTCAGGACCCGCGGCCCCTGTCCCCTGGGGCCTTGCAGCTT
GCTGGAGAGAAGAGCAGTGAGAAGGGCCTGAGAGAGCGCGCCTACGGCAGCAGCGGGGAG
CTCATCACCAGCCTGCCCATCAGCATCCCGCTCAGCACCGTGCAGCCCAACAAGCTCCCG
GTCAGCATTCCCCTGGCCAGCGTGGTGCTGCCCAGCCGCGCCGAGAGGGCGAGGAGCACC
CCCAGTCCCGTGCTGCAGCCCCGTGACCCCTCGTCCACACTTGAAAAGCAGATTGGTGCT
AATGCCCACGGTGCTGGGAGCAGAAGCCTTGCCCTGGCCCCCGCAGGCTTCTCCTACGCT
GGCTCGGTGGCCATCAGCGGGGCCTTGGCGGGCAGCCCGGCCTCTCTCACACCTGGAGCC
GAGCCGGCCACCTTGGATGAGTCCTCCAGCTCTGGGAGCCTTTTTGCCACCGTGGGGTCC
CGCAGCTCCACGCCACAGCACCCCCTGCTGCTGGCACAGCCCCGGAACTCGCTTCCTGCC
TCTCCCGCCCACCAGCTCTCCTCCAGTCCCCGGCTTGGTGGGGCCGCCCAGGGCCCGTTG
CCCGAGGCCAGCAAGGGAGACCTGCCCTCCGATTCCGGCTTCTCAGATCCTGAGAGTGAA
GCCAAGAGGAGGATTGTGTTCACCATCACCACTGGTGCGGGCAGTGCCAAGCAGTCGCCC
TCCAGCAAGCACAGCCCCCTGACCGCCAGCGCCCGTGGGGACTGTGTGCCGAGCCACGGG
CAGGACAGTCGCAGGCGCGGCCGGCGGAAGCGAGCATCTGCGGGGACGCCCAGCTTGAGC
GCAGGCGTGTCCCCCAAGCGCCGAGCCCTGCCGTCCGTCGCTGGCCTTTTCACACAGCCT
TCGGGGTCTCCCCTCAACCTCAACTCCATGGTCAGTAACATCAACCAGCCCCTGGAGATT
ACAGCCATCTCGTCCCCGGAGACCTCCCTGAAGAGCTCCCCTGTGCCCTACCAGGACCAC
GACCAGCCCCCCGTGCTCAAGAAGGAGCGGCCTCTGAGCCAGACCAATGGGGCACACTAC
TCCCCACTCACCTCAGACGAGGAGCCAGGCTCTGAGGACGAGCCCAGCAGTGCTCGAATT
GAGAGAAAAATTGCAACAATCTCCTTAGAAAGCAAATCTCCCCCGAAAACCTTGGAAAAT
GGTGGTGGCTTGGCGGGAAGGAAGCCCGCGCCCGCCGGCGAGCCAGTCAATAGCAGCAAG
TGGAAGTCCACCTTCTCGCCCATCTCCGACATCGGCCTGGCCAAGTCGGCGGACAGCCCG
CTGCAGGCCAGCTCCGCCCTCAGCCAGAACTCCCTGTTCACGTTCCGGCCCGCCCTGGAG
GAGCCCTCTGCCGATGCCAAGCTGGCCGCTCACCCCAGGAAAGGCTTTCCCGGCTCCCTG
TCGGGGGCTGACGGACTCAGCCCGGGCACCAACCCTGCCAACGGCTGCACCTTCGGCGGG
GGCCTGGCCGCGGACCTGAGTTTACACAGCTTCAGTGATGGTGCTTCTCTTCCCCACAAG
GGCCCCGAGGCGGCCGGCCTGAGCTCCCCGCTGAGCTTCCCCTCGCAGCGCGGCAAGGAG
GGCTCGGACGCCAACCCTTTCCTGAGCAAGAGGCAGCTGGACGGCCTGGCTGGGCTGAAG
GGCGAGGGCAGCCGCGGCAAGGAGGCAGGGGAGGGCGGCCTACCGCTGTGCGGGCCCACG
GACAAGACCCCACTGCTGAGCGGCAAGGCCGCCAAGGCCCGGGACCGCGAGGTCGACCTC
AAGAATGGCCACAACCTCTTCATCTCTGCGGCGGCCGTGCCTCCCGGAAGCCTCCTCAGC
GGCCCCGGCCTGGCCCCGGCGGCGTCCTCCGCAGGCGGCGCGGCGTCCTCCGCCCAGACG
CACCGGTCCTTCCTGGGCCCCTTCCCGCCGGGACCGCAGTTCGCGCTCGGCCCCATGTCC
CTGCAGGCCAACCTCGGCTCCGTGGCCGGCTCCTCCGTGCTGCAGTCGCTGTTCAGCTCT
GTGCCGGCCGCCGCAGGCCTGGTGCACGTGTCGTCCGCTGCCACCAGACTGACCAACTCG
CACGCCATGGGCAGCTTTTCCGGGGTGGCAGGCGGCACAGTTGGAGGTAACTAG
GenBank Gene IDAK074120
GeneCard IDNot Available
GenAtlas IDDOT1L
HGNC IDHGNC:24948
Chromosome Location19
Locus19p13.3
References
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  2. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. 15057824
  3. Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O: Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 2001 Apr 27;8(2):85-95. 11347906
  4. Jikuya H, Takano J, Kikuno R, Hirosawa M, Nagase T, Nomura N, Ohara O: Characterization of long cDNA clones from human adult spleen. II. The complete sequences of 81 cDNA clones. DNA Res. 2003 Feb 28;10(1):49-57. 12693554
  5. Okada Y, Feng Q, Lin Y, Jiang Q, Li Y, Coffield VM, Su L, Xu G, Zhang Y: hDOT1L links histone methylation to leukemogenesis. Cell. 2005 Apr 22;121(2):167-78. 15851025
  6. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. 18220336
  7. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  8. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  9. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  10. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  11. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
  12. Min J, Feng Q, Li Z, Zhang Y, Xu RM: Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase. Cell. 2003 Mar 7;112(5):711-23. 12628190