• Gene id: 84444

Gene Summary

• Gene Symbol: DOT1L   Gene   UCSC   Ensembl
• Aliases: DOT1, KMT4
• Gene name: DOT1 like histone lysine methyltransferase
• Alternate names: histone-lysine N-methyltransferase, H3 lysine-79 specific, DOT1 like histone H3K79 methyltransferase, DOT1-like histone methyltransferase, DOT1-like protein, DOT1-like, histone H3 methyltransferase, H3-K79-HMTase, histone H3-K79 methyltransferase, histone methyl,
• Gene location: 19p13.3 (2163932: 2232577)     Exons: 9     NC_000019.10
• Gene summary(Entrez): The protein encoded by this gene is a histone methyltransferase that methylates lysine-79 of histone H3. It is inactive against free core histones, but shows significant histone methyltransferase activity against nucleosomes. [provided by RefSeq, Aug 2011
• OMIM: 607375

Protein Summary

• Protein general information: Q8TEK3  
  • Name: Histone lysine N methyltransferase, H3 lysine 79 specific (EC 2.1.1.360) (DOT1 like protein) (Histone H3 K79 methyltransferase) (H3 K79 HMTase) (Lysine N methyltransferase 4)
  • Length: 1537  
  • Mass: 164856
• Sequence:

  MGEKLELRLKSPVGAEPAVYPWPLPVYDKHHDAAHEIIETIRWVCEEIPDLKLAMENYVLIDYDTKSFESMQRLC
  DKYNRAIDSIHQLWKGTTQPMKLNTRPSTGLLRHILQQVYNHSVTDPEKLNNYEPFSPEVYGETSFDLVAQMIDE
  IKMTDDDLFVDLGSGVGQVVLQVAAATNCKHHYGVEKADIPAKYAETMDREFRKWMKWYGKKHAEYTLERGDFLS
  EEWRERIANTSVIFVNNFAFGPEVDHQLKERFANMKEGGRIVSSKPFAPLNFRINSRNLSDIGTIMRVVELSPLK
  GSVSWTGKPVSYYLHTIDRTILENYFSSLKNPKLREEQEAARRRQQRESKSNAATPTKGPEGKVAGPADAPMDSG
  AEEEKAGAATVKKPSPSKARKKKLNKKGRKMAGRKRGRPKKMNTANPERKPKKNQTALDALHAQTVSQTAASSPQ
  DAYRSPHSPFYQLPPSVQRHSPNPLLVAPTPPALQKLLESFKIQYLQFLAYTKTPQYKASLQELLGQEKEKNAQL
  LGAAQQLLSHCQAQKEEIRRLFQQKLDELGVKALTYNDLIQAQKEISAHNQQLREQSEQLEQDNRALRGQSLQLL
  KARCEELQLDWATLSLEKLLKEKQALKSQISEKQRHCLELQISIVELEKSQRQQELLQLKSCVPPDDALSLHLRG
  KGALGRELEPDASRLHLELDCTKFSLPHLSSMSPELSMNGQAAGYELCGVLSRPSSKQNTPQYLASPLDQEVVPC
  TPSHVGRPRLEKLSGLAAPDYTRLSPAKIVLRRHLSQDHTVPGRPAASELHSRAEHTKENGLPYQSPSVPGSMKL
  SPQDPRPLSPGALQLAGEKSSEKGLRERAYGSSGELITSLPISIPLSTVQPNKLPVSIPLASVVLPSRAERARST
  PSPVLQPRDPSSTLEKQIGANAHGAGSRSLALAPAGFSYAGSVAISGALAGSPASLTPGAEPATLDESSSSGSLF
  ATVGSRSSTPQHPLLLAQPRNSLPASPAHQLSSSPRLGGAAQGPLPEASKGDLPSDSGFSDPESEAKRRIVFTIT
  TGAGSAKQSPSSKHSPLTASARGDCVPSHGQDSRRRGRRKRASAGTPSLSAGVSPKRRALPSVAGLFTQPSGSPL
  NLNSMVSNINQPLEITAISSPETSLKSSPVPYQDHDQPPVLKKERPLSQTNGAHYSPLTSDEEPGSEDEPSSARI
  ERKIATISLESKSPPKTLENGGGLAGRKPAPAGEPVNSSKWKSTFSPISDIGLAKSADSPLQASSALSQNSLFTF
  RPALEEPSADAKLAAHPRKGFPGSLSGADGLSPGTNPANGCTFGGGLAADLSLHSFSDGASLPHKGPEAAGLSSP
  LSFPSQRGKEGSDANPFLSKRQLDGLAGLKGEGSRGKEAGEGGLPLCGPTDKTPLLSGKAAKARDREVDLKNGHN
  LFISAAAVPPGSLLSGPGLAPAASSAGGAASSAQTHRSFLGPFPPGPQFALGPMSLQANLGSVAGSSVLQSLFSS
  VPAAAGLVHVSSAATRLTNSHAMGSFSGVAGGTVGGN

• Structural information:
  • Protein Domains: (16..33-)
    (/note="DOT1-)
    (/evidence="ECO:0000255|PROSITE-ProRule:PRU00902"-)
  • Interpro: IPR025789  IPR021169  IPR030445  IPR029063  
  • Prosite: PS51569
  • PDB: 1NW3 2MV7 3QOW 3QOX 3SR4 3SX0 3UWP 4EK9 4EKG 4EKI 4EQZ 4ER0 4ER3 4ER5 4ER6 4ER7 4HRA 4WVL 5DRT 5DRY 5DSX 5DT2 5DTM 5DTQ 5DTR 5JUW 5MVS 5MW3 5MW4 6IN3 6J99 6JM9 6JMA 6JN2 6NJ9 6NN6 6NOG 6NQA 6O96 6TE6 6TEL 6TEN
  • PDBsum: 1NW3 2MV7 3QOW 3QOX 3SR4 3SX0 3UWP 4EK9 4EKG 4EKI 4EQZ 4ER0 4ER3 4ER5 4ER6 4ER7 4HRA 4WVL 5DRT 5DRY 5DSX 5DT2 5DTM 5DTQ 5DTR 5JUW 5MVS 5MW3 5MW4 6IN3 6J99 6JM9 6JMA 6JN2 6NJ9 6NN6 6NOG 6NQA 6O96 6TE6 6TEL 6TEN
  • DIP: 56410
  • STRING: ENSP00000381657
• Other Databases: GeneCards:  DOT1L  Malacards:  DOT1L

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:2000677	regulation of transcription regulatory region DNA binding	IBA	biological process
GO:0031151	histone methyltransferase activity (H3-K79 specific)	IBA	molecular function
GO:0005634	nucleus	IBA	cellular component
GO:0006348	chromatin silencing at telomere	IBA	biological process
GO:0006281	DNA repair	IBA	biological process
GO:0000077	DNA damage checkpoint	IBA	biological process
GO:0018024	histone-lysine N-methyltransferase activity	IDA	molecular function
GO:0018024	histone-lysine N-methyltransferase activity	IEA	molecular function
GO:0034729	histone H3-K79 methylation	IEA	biological process
GO:0051726	regulation of cell cycle	IEA	biological process
GO:0005634	nucleus	IEA	cellular component
GO:0006342	chromatin silencing	IEA	biological process
GO:0031151	histone methyltransferase activity (H3-K79 specific)	IEA	molecular function
GO:0016740	transferase activity	IEA	molecular function
GO:0032259	methylation	IEA	biological process
GO:0006325	chromatin organization	IEA	biological process
GO:0005634	nucleus	IEA	cellular component
GO:0003677	DNA binding	IEA	molecular function
GO:0008168	methyltransferase activity	IEA	molecular function
GO:0034729	histone H3-K79 methylation	IDA	biological process
GO:0032991	protein-containing complex	IDA	cellular component
GO:0008284	positive regulation of cell population proliferation	IDA	biological process
GO:0045944	positive regulation of transcription by RNA polymerase II	IDA	biological process
GO:0042054	histone methyltransferase activity	IDA	molecular function
GO:0005634	nucleus	IDA	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0018024	histone-lysine N-methyltransferase activity	TAS	molecular function
GO:0018024	histone-lysine N-methyltransferase activity	TAS	molecular function
GO:0018024	histone-lysine N-methyltransferase activity	TAS	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0042054	histone methyltransferase activity	IEA	molecular function
GO:0032200	telomere organization	TAS	biological process
GO:0005634	nucleus	IEA	cellular component
GO:0005654	nucleoplasm	IDA	cellular component
GO:0043231	intracellular membrane-bounded organelle	IDA	cellular component
GO:0000781	chromosome, telomeric region	IEA	cellular component
GO:0046425	regulation of receptor signaling pathway via JAK-STAT	IDA	biological process
GO:2000677	regulation of transcription regulatory region DNA binding	IMP	biological process

KEGG pathways

Pathway id	Pathway name
hsa01100	Metabolic pathways
hsa05202	Transcriptional misregulation in cancer
hsa00310	Lysine degradation

Diseases

Associated diseases	References
B- and T-cell mixed leukemia	PMID:23801631
Cryptorchidism	MIK: 28606200
Hypospermatogenesis	MIK: 28361989
Non obstructive azoospermia	MIK: 24012201
Sertoli cell only syndrome	MIK: 23869807
Teratozoospermia	MIK: 17327269

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
24012201	Non obstructive azoospermia			31 (4 controls, 27 cases)	Male infertility	GSE45885 analyzed by GEO2R (cutoff 1.5 fold)
17327269	Teratozoospermia			19 (6 controls, 13 cases)	Male infertility	GSE6872 analyzed by GEO2R (cutoff 1.5 fold)
23869807	Non obstructive azoospermia, Sertoli cell only syndrome			20 (4 controls, 16 cases)	Male infertility	GSE45887 analyzed by GEO2R (cutoff 1.5 fold)
28606200	Cryptorchidism			Monozgotic twins (1 control, I cwith cryptorchidism)	Male infertility	MeDIP-Seq
28361989	Hypospermatogenesis			6 (3 controls, 3 Klienfelter syndrome	Male infertility	Microarray