DOT1L
entrez
84444
canonical
uniprot
Q8TEK3
canonical
ensembl
ENSG00000104885
resolver
ensp
ENSP00000381657
resolver
ensp
ENSP00000510335
resolver
enst
ENST00000686010
resolver
genesymbol
DOT1L
resolver
genesymbol_syn
KIAA1814
resolver
genesymbol_syn
KMT4
resolver
hgnc
HGNC:24948
resolver
uniprot
A0A8I5QL06
resolver
uniprot
O60379
resolver
uniprot
Q96JL1
resolver
uniprot_entry
A0A8I5QL06_HUMAN
resolver
uniprot_entry
DOT1L_HUMAN
resolver
uniprot_sec
O60379
resolver
uniprot_sec
Q96JL1
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by EPZ00477747 compound, a chemical derivative of S-adenosyl-L-methionine (SAM). {ECO:0000269|PubMed:38129415}.
uniprot
proteins
amino_acid_sequence
MGEKLELRLKSPVGAEPAVYPWPLPVYDKHHDAAHEIIETIRWVCEEIPDLKLAMENYVLIDYDTKSFESMQRLCDKYNRAIDSIHQLWKGTTQPMKLNTRPSTGLLRHILQQVYNHSVTDPEKLNNYEPFSPEVYGETSFDLVAQMIDEIKMTDDDLFVDLGSGVGQVVLQVAAATNCKHHYGVEKADIPAKYAETMDREFRKWMKWYGKKHAEYTLERGDFLSEEWRERIANTSVIFVNNFAFGPEVDHQLKERFANMKEGGRIVSSKPFAPLNFRINSRNLSDIGTIMRVVELSPLKGSVSWTGKPVSYYLHTIDRTILENYFSSLKNPKLREEQEAARRRQQRESKSNAATPTKGPEGKVAGPADAPMDSGAEEEKAGAATVKKPSPSKARKKKLNKKGRKMAGRKRGRPKKMNTANPERKPKKNQTALDALHAQTVSQTAASSPQDAYRSPHSPFYQLPPSVQRHSPNPLLVAPTPPALQKLLESFKIQYLQFLAYTKTPQYKASLQELLGQEKEKNAQLLGAAQQLLSHCQAQKEEIRRLFQQKLDELGVKALTYNDLIQAQKEISAHNQQLREQSEQLEQDNRALRGQSLQLLKARCEELQLDWATLSLEKLLKEKQALKSQISEKQRHCLELQISIVELEKSQRQQELLQLKSCVPPDDALSLHLRGKGALGRELEPDASRLHLELDCTKFSLPHLSSMSPELSMNGQAAGYELCGVLSRPSSKQNTPQYLASPLDQEVVPCTPSHVGRPRLEKLSGLAAPDYTRLSPAKIVLRRHLSQDHTVPGRPAASELHSRAEHTKENGLPYQSPSVPGSMKLSPQDPRPLSPGALQLAGEKSSEKGLRERAYGSSGELITSLPISIPLSTVQPNKLPVSIPLASVVLPSRAERARSTPSPVLQPRDPSSTLEKQIGANAHGAGSRSLALAPAGFSYAGSVAISGALAGSPASLTPGAEPATLDESSSSGSLFATVGSRSSTPQHPLLLAQPRNSLPASPAHQLSSSPRLGGAAQGPLPEASKGDLPSDSGFSDPESEAKRRIVFTITTGAGSAKQSPSSKHSPLTASARGDCVPSHGQDSRRRGRRKRASAGTPSLSAGVSPKRRALPSVAGLFTQPSGSPLNLNSMVSNINQPLEITAISSPETSLKSSPVPYQDHDQPPVLKKERPLSQTNGAHYSPLTSDEEPGSEDEPSSARIERKIATISLESKSPPKTLENGGGLAGRKPAPAGEPVNSSKWKSTFSPISDIGLAKSADSPLQASSALSQNSLFTFRPALEEPSADAKLAAHPRKGFPGSLSGADGLSPGTNPANGCTFGGGLAADLSLHSFSDGASLPHKGPEAAGLSSPLSFPSQRGKEGSDANPFLSKRQLDGLAGLKGEGSRGKEAGEGGLPLCGPTDKTPLLSGKAAKARDREVDLKNGHNLFISAAAVPPGSLLSGPGLAPAASSAGGAASSAQTHRSFLGPFPPGPQFALGPMSLQANLGSVAGSSVLQSLFSSVPAAAGLVHVSSAATRLTNSHAMGSFSGVAGGTVGGN
uniprot
proteins
disease_involvement
DISEASE: Nil-Deshwar neurodevelopmental syndrome (NDNS) [MIM:621265]: An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, impaired intellectual development, poor or absent speech, hypotonia, and various heterogeneous congenital anomalies, including brain, cardiac and urogenital abnormalities. {ECO:0000269|PubMed:37827158}. Note=The disease is caused by variants affecting the gene represented in this entry. Disease-causing variants may act through a gain-of-function effect leading to an increase in cellular H3K79 methylation levels. {ECO:0000269|PubMed:37827158}.
uniprot
proteins
ec_number
2.1.1.360
uniprot
proteins
function
FUNCTION: Histone methyltransferase that methylates 'Lys-79' of histone H3 (PubMed:12123582, PubMed:38503750, PubMed:38129415). Histones in nucleosomes are preferred as substrate compared to free histones (PubMed:12123582, PubMed:38503750). Binds to DNA (PubMed:12628190, PubMed:38503750). Together with MLLT3/AF9, is involved in SCNN1A transcriptional repression following H3K79 hypermethylation at the promoter (By similarity). {ECO:0000250|UniProtKB:Q6XZL8, ECO:0000269|PubMed:12123582, ECO:0000269|PubMed:12628190, ECO:0000269|PubMed:38129415, ECO:0000269|PubMed:38503750}.
uniprot
proteins
mass_dalton
164856
uniprot
proteins
mutagenesis
MUTAGEN 163..165; /note="GSG->RCR: Abolishes methyltransferase activity."; /evidence="ECO:0000269|PubMed:12123582"; MUTAGEN 241; /note="N->A,D: Loss of activity."; /evidence="ECO:0000269|PubMed:12628190"; MUTAGEN 270; /note="K->D: Reduces methyltransferase activity."; /evidence="ECO:0000269|PubMed:38503750"; MUTAGEN 312; /note="Y->A: Loss of activity."; /evidence="ECO:0000269|PubMed:12628190"; MUTAGEN 312; /note="Y->F: No effect."; /evidence="ECO:0000269|PubMed:12628190
uniprot
proteins
protein_family
Class I-like SAM-binding methyltransferase superfamily
uniprot
proteins
protein_family
DOT1 family
uniprot
proteins
pubmed
11347906
uniprot
proteins
pubmed
12123582
uniprot
proteins
pubmed
12628190
uniprot
proteins
pubmed
12693554
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15851025
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
37827158
uniprot
proteins
pubmed
38129415
uniprot
proteins
pubmed
38270553
uniprot
proteins
pubmed
38503750
uniprot
proteins
sequence_length
1537
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15851025}. Cytoplasm {ECO:0000250|UniProtKB:Q6XZL8}. Note=Cytoplasmic localization is dependent on and mediated by MLLT6/AF17. {ECO:0000250|UniProtKB:Q6XZL8}.
uniprot
proteins