Q8TEK3 · DOT1L_HUMAN

  • Protein
    Histone-lysine N-methyltransferase, H3 lysine-79 specific
  • Gene
    DOT1L
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones (PubMed:12123582).
Binds to DNA (PubMed:12628190).

Miscellaneous

In contrast to other lysine histone methyltransferases, it does not contain a SET domain, suggesting the existence of another mechanism for methylation of lysine residues of histones.

Catalytic activity

Features

Showing features for binding site.

115372004006008001,0001,2001,400
TypeIDPosition(s)Description
Binding site136-139S-adenosyl-L-methionine (UniProtKB | ChEBI)
Binding site159-168S-adenosyl-L-methionine (UniProtKB | ChEBI)
Binding site186S-adenosyl-L-methionine (UniProtKB | ChEBI)
Binding site222-223S-adenosyl-L-methionine (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentintracellular membrane-bounded organelle
Cellular Componentnucleoplasm
Cellular Componentnucleus
Cellular Componentprotein-containing complex
Molecular FunctionDNA binding
Molecular Functionhistone H3 methyltransferase activity
Molecular Functionhistone H3K79 methyltransferase activity
Molecular Functionhistone H3K79 trimethyltransferase activity
Molecular Functionhistone methyltransferase activity
Molecular Functionnucleic acid binding
Molecular FunctionRNA polymerase II-specific DNA-binding transcription factor binding
Molecular Functiontranscription coactivator activity
Biological ProcessDNA damage checkpoint signaling
Biological ProcessDNA repair
Biological Processgene expression
Biological Processheterochromatin formation
Biological Processmethylation
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processregulation of receptor signaling pathway via JAK-STAT
Biological Processregulation of transcription regulatory region DNA binding
Biological Processtelomere organization

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Histone-lysine N-methyltransferase, H3 lysine-79 specific
  • EC number
  • Alternative names
    • DOT1-like protein
    • Histone H3-K79 methyltransferase (H3-K79-HMTase)
    • Lysine N-methyltransferase 4

Gene names

    • Name
      DOT1L
    • Synonyms
      KIAA1814, KMT4

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q8TEK3
  • Secondary accessions
    • O60379
    • Q96JL1

Proteomes

Organism-specific databases

Disease & Variants

Involvement in disease

  • Defects in DOTL1 are associated with an autosomal dominant form of global developmental delay and intellectual disability, with or without one or more major congenital anomalies (PubMed:37827158). The patient phenotypes are characterized by central nervous system (CNS) dysfunction, such as mild motor delay and significant speech and language delay, and a range of congenital anomalies, including brain structural anomalies, cardiac defects, varied urogenital features and growth restriction (PubMed:37827158). Variants may cause a gain-of-function effect leading to an increase in cellular H3K79 methylation levels (PubMed:37827158)

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_08867945found in a patient with developmental delay and intellectual disability; uncertain significance
Natural variantVAR_088680100found in a patient with developmental delay and intellectual disability; likely pathogenic; dbSNP:rs781606489
Natural variantVAR_088681123found in patients with developmental delay and intellectual disability; likely pathogenic; causes an almost 4-fold increase in H3K79 methylation in vitro; dbSNP:rs2022775856
Natural variantVAR_088682129found in a patient with developmental delay and intellectual disability; likely pathogenic; dbSNP:rs2144742354
Mutagenesis163-165Abolishes methyltransferase activity.
Mutagenesis241Loss of activity.
Natural variantVAR_088683292in dbSNP:rs2144814855
Mutagenesis312Loss of activity.
Mutagenesis312No effect.
Natural variantVAR_088684451in dbSNP:rs377185393
Natural variantVAR_088685626found in a patient with developmental delay and intellectual disability; likely pathogenic
Natural variantVAR_014287726in dbSNP:rs880525
Natural variantVAR_088686853found in a patient with developmental delay and intellectual disability; likely pathogenic; slightly increases H3K79 methylation in vitro; dbSNP:rs1599605821
Natural variantVAR_0886871025found in a patient with developmental delay and intellectual disability; uncertain significance; dbSNP:rs753193665
Natural variantVAR_0142881386in dbSNP:rs3815308
Natural variantVAR_0142891418in dbSNP:rs2302061

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 2,580 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
ChainPRO_00001860891-1537UniProtHistone-lysine N-methyltransferase, H3 lysine-79 specific
Modified residue297UniProtPhosphoserine
Modified residue (large scale data)297PRIDEPhosphoserine
Modified residue374UniProtPhosphoserine
Modified residue (large scale data)374PRIDEPhosphoserine
Modified residue (large scale data)390PRIDEPhosphoserine
Modified residue (large scale data)392PRIDEPhosphoserine
Modified residue (large scale data)447PRIDEPhosphoserine
Modified residue448UniProtPhosphoserine
Modified residue (large scale data)448PRIDEPhosphoserine
Modified residue (large scale data)458PRIDEPhosphoserine
Modified residue471UniProtPhosphoserine
Modified residue (large scale data)471PRIDEPhosphoserine
Modified residue480UniProtPhosphothreonine
Modified residue (large scale data)480PRIDEPhosphothreonine
Modified residue (large scale data)764PRIDEPhosphoserine
Modified residue (large scale data)772PRIDEPhosphothreonine
Modified residue775UniProtPhosphoserine
Modified residue (large scale data)775PRIDEPhosphoserine
Modified residue786UniProtPhosphoserine
Modified residue (large scale data)786PRIDEPhosphoserine
Modified residue (large scale data)816PRIDEPhosphoserine
Modified residue826UniProtPhosphoserine
Modified residue (large scale data)826PRIDEPhosphoserine
Modified residue834UniProtPhosphoserine; by MAPK11
Modified residue (large scale data)834PRIDEPhosphoserine
Modified residue (large scale data)899PRIDEPhosphoserine
Modified residue900UniProtPhosphothreonine; by MAPK11
Modified residue (large scale data)900PRIDEPhosphothreonine
Modified residue902UniProtPhosphoserine; by MAPK11
Modified residue (large scale data)902PRIDEPhosphoserine
Modified residue984UniProtPhosphothreonine; by MAPK11
Modified residue (large scale data)984PRIDEPhosphothreonine
Modified residue997UniProtPhosphoserine
Modified residue (large scale data)997PRIDEPhosphoserine
Modified residue1001UniProtPhosphoserine; by MAPK11
Modified residue (large scale data)1001PRIDEPhosphoserine
Modified residue (large scale data)1007PRIDEPhosphoserine
Modified residue (large scale data)1008PRIDEPhosphoserine
Modified residue1009UniProtPhosphoserine; by MAPK11
Modified residue (large scale data)1009PRIDEPhosphoserine
Modified residue (large scale data)1030PRIDEPhosphoserine
Modified residue (large scale data)1032PRIDEPhosphoserine
Modified residue1035UniProtPhosphoserine
Modified residue (large scale data)1035PRIDEPhosphoserine
Modified residue (large scale data)1039PRIDEPhosphoserine
Modified residue (large scale data)1059PRIDEPhosphoserine
Modified residue (large scale data)1061PRIDEPhosphoserine
Modified residue (large scale data)1065PRIDEPhosphoserine
Modified residue (large scale data)1083PRIDEPhosphoserine
Modified residue1093UniProtPhosphoserine
Modified residue (large scale data)1093PRIDEPhosphoserine
Modified residue (large scale data)1096PRIDEPhosphothreonine
Modified residue (large scale data)1100PRIDEPhosphoserine
Modified residue1104UniProtPhosphoserine; by MAPK11
Modified residue (large scale data)1104PRIDEPhosphoserine
Modified residue (large scale data)1152PRIDEPhosphoserine
Modified residue (large scale data)1153PRIDEPhosphoserine
Modified residue (large scale data)1208PRIDEPhosphoserine
Modified residue (large scale data)1211PRIDEPhosphoserine
Modified residue1213UniProtPhosphoserine
Modified residue (large scale data)1213PRIDEPhosphoserine
Modified residue1246UniProtPhosphoserine
Modified residue (large scale data)1246PRIDEPhosphoserine
Modified residue (large scale data)1259PRIDEPhosphoserine
Modified residue (large scale data)1348PRIDEPhosphoserine
Modified residue (large scale data)1349PRIDEPhosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Organism-specific databases

Interaction

Subunit

Interacts with MLLT10.

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q8TEK3MLLT1 Q031116EBI-2619253, EBI-1384215
BINARY Q8TEK3MLLT3 P425686EBI-2619253, EBI-716132

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for domain, compositional bias, region.

TypeIDPosition(s)Description
Domain16-330DOT1
Compositional bias334-349Basic and acidic residues
Region334-467Disordered
Compositional bias390-415Basic residues
Region391-416Required for interaction with nucleosomes and DNA
Compositional bias416-431Basic and acidic residues
Compositional bias433-467Polar residues
Region785-853Disordered
Compositional bias809-823Polar residues
Region893-912Disordered
Region957-1128Disordered
Compositional bias962-991Polar residues
Compositional bias998-1012Polar residues
Compositional bias1051-1068Polar residues
Region1145-1243Disordered
Region1334-1410Disordered

Sequence similarities

Belongs to the class I-like SAM-binding methyltransferase superfamily. DOT1 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

Q8TEK3-2

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    1,537
  • Mass (Da)
    164,856
  • Last updated
    2018-09-12 v3
  • Checksum
    9CEA12850DC4ACB1
MGEKLELRLKSPVGAEPAVYPWPLPVYDKHHDAAHEIIETIRWVCEEIPDLKLAMENYVLIDYDTKSFESMQRLCDKYNRAIDSIHQLWKGTTQPMKLNTRPSTGLLRHILQQVYNHSVTDPEKLNNYEPFSPEVYGETSFDLVAQMIDEIKMTDDDLFVDLGSGVGQVVLQVAAATNCKHHYGVEKADIPAKYAETMDREFRKWMKWYGKKHAEYTLERGDFLSEEWRERIANTSVIFVNNFAFGPEVDHQLKERFANMKEGGRIVSSKPFAPLNFRINSRNLSDIGTIMRVVELSPLKGSVSWTGKPVSYYLHTIDRTILENYFSSLKNPKLREEQEAARRRQQRESKSNAATPTKGPEGKVAGPADAPMDSGAEEEKAGAATVKKPSPSKARKKKLNKKGRKMAGRKRGRPKKMNTANPERKPKKNQTALDALHAQTVSQTAASSPQDAYRSPHSPFYQLPPSVQRHSPNPLLVAPTPPALQKLLESFKIQYLQFLAYTKTPQYKASLQELLGQEKEKNAQLLGAAQQLLSHCQAQKEEIRRLFQQKLDELGVKALTYNDLIQAQKEISAHNQQLREQSEQLEQDNRALRGQSLQLLKARCEELQLDWATLSLEKLLKEKQALKSQISEKQRHCLELQISIVELEKSQRQQELLQLKSCVPPDDALSLHLRGKGALGRELEPDASRLHLELDCTKFSLPHLSSMSPELSMNGQAAGYELCGVLSRPSSKQNTPQYLASPLDQEVVPCTPSHVGRPRLEKLSGLAAPDYTRLSPAKIVLRRHLSQDHTVPGRPAASELHSRAEHTKENGLPYQSPSVPGSMKLSPQDPRPLSPGALQLAGEKSSEKGLRERAYGSSGELITSLPISIPLSTVQPNKLPVSIPLASVVLPSRAERARSTPSPVLQPRDPSSTLEKQIGANAHGAGSRSLALAPAGFSYAGSVAISGALAGSPASLTPGAEPATLDESSSSGSLFATVGSRSSTPQHPLLLAQPRNSLPASPAHQLSSSPRLGGAAQGPLPEASKGDLPSDSGFSDPESEAKRRIVFTITTGAGSAKQSPSSKHSPLTASARGDCVPSHGQDSRRRGRRKRASAGTPSLSAGVSPKRRALPSVAGLFTQPSGSPLNLNSMVSNINQPLEITAISSPETSLKSSPVPYQDHDQPPVLKKERPLSQTNGAHYSPLTSDEEPGSEDEPSSARIERKIATISLESKSPPKTLENGGGLAGRKPAPAGEPVNSSKWKSTFSPISDIGLAKSADSPLQASSALSQNSLFTFRPALEEPSADAKLAAHPRKGFPGSLSGADGLSPGTNPANGCTFGGGLAADLSLHSFSDGASLPHKGPEAAGLSSPLSFPSQRGKEGSDANPFLSKRQLDGLAGLKGEGSRGKEAGEGGLPLCGPTDKTPLLSGKAAKARDREVDLKNGHNLFISAAAVPPGSLLSGPGLAPAASSAGGAASSAQTHRSFLGPFPPGPQFALGPMSLQANLGSVAGSSVLQSLFSSVPAAAGLVHVSSAATRLTNSHAMGSFSGVAGGTVGGN

Q8TEK3-1

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1537-1537: N → VVFNHAVPSASAHPFGARVGRGAACGSATLGPSPLQAAASASASSFQAPASVETRPPPPPPPPPPPLPPPAHLGRSPAGPPVLHAPPPPNAALPPPPTLLASNPEPALLQSLASLPPNQAFLPPTSAASLPPANASLSIKLTSLPHKGARPSFTVHHQPLPRLALAQAAPGIPQASATGPSAVWVSLGMPPPYAAHLSGVKPR

Computationally mapped potential isoform sequences

There are 5 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8I5QL06A0A8I5QL06_HUMANDOT1L1738
C9JH95C9JH95_HUMANDOT1L208
V9GY76V9GY76_HUMANDOT1L142
H7C2S2H7C2S2_HUMANDOT1L653
A0A087X1A7A0A087X1A7_HUMANDOT1L69

Sequence caution

The sequence AAC08316.1 differs from that shown. Reason: Erroneous gene model prediction

Features

Showing features for sequence conflict, compositional bias, alternative sequence.

TypeIDPosition(s)Description
Sequence conflict210in Ref. 4; BAB84946
Compositional bias334-349Basic and acidic residues
Compositional bias390-415Basic residues
Compositional bias416-431Basic and acidic residues
Compositional bias433-467Polar residues
Sequence conflict454-467in Ref. 3
Sequence conflict464in Ref. 4; BAB84946
Compositional bias809-823Polar residues
Compositional bias962-991Polar residues
Compositional bias998-1012Polar residues
Compositional bias1051-1068Polar residues
Alternative sequenceVSP_0597951537in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF509504
EMBL· GenBank· DDBJ
AAM88322.1
EMBL· GenBank· DDBJ
mRNA
AC004490
EMBL· GenBank· DDBJ
AAC08316.1
EMBL· GenBank· DDBJ
Genomic DNA Sequence problems.
AB058717
EMBL· GenBank· DDBJ
BAB47443.1
EMBL· GenBank· DDBJ
mRNA
AK074120
EMBL· GenBank· DDBJ
BAB84946.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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