DOT1L

Protein identityUniProt · HPA

UniProt accession

Q8TEK3

Gene

DOT1L

Ensembl

ENSG00000104885

Chromosome

19

Canonical length

1537 aa

Protein class

Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1537 residues, UniProt reviewed canonical sequence.

>Q8TEK3|DOT1L
     1  MGEKLELRLK SPVGAEPAVY PWPLPVYDKH HDAAHEIIET IRWVCEEIPD LKLAMENYVL
    61  IDYDTKSFES MQRLCDKYNR AIDSIHQLWK GTTQPMKLNT RPSTGLLRHI LQQVYNHSVT
   121  DPEKLNNYEP FSPEVYGETS FDLVAQMIDE IKMTDDDLFV DLGSGVGQVV LQVAAATNCK
   181  HHYGVEKADI PAKYAETMDR EFRKWMKWYG KKHAEYTLER GDFLSEEWRE RIANTSVIFV
   241  NNFAFGPEVD HQLKERFANM KEGGRIVSSK PFAPLNFRIN SRNLSDIGTI MRVVELSPLK
   301  GSVSWTGKPV SYYLHTIDRT ILENYFSSLK NPKLREEQEA ARRRQQRESK SNAATPTKGP
   361  EGKVAGPADA PMDSGAEEEK AGAATVKKPS PSKARKKKLN KKGRKMAGRK RGRPKKMNTA
   421  NPERKPKKNQ TALDALHAQT VSQTAASSPQ DAYRSPHSPF YQLPPSVQRH SPNPLLVAPT
   481  PPALQKLLES FKIQYLQFLA YTKTPQYKAS LQELLGQEKE KNAQLLGAAQ QLLSHCQAQK
   541  EEIRRLFQQK LDELGVKALT YNDLIQAQKE ISAHNQQLRE QSEQLEQDNR ALRGQSLQLL
   601  KARCEELQLD WATLSLEKLL KEKQALKSQI SEKQRHCLEL QISIVELEKS QRQQELLQLK
   661  SCVPPDDALS LHLRGKGALG RELEPDASRL HLELDCTKFS LPHLSSMSPE LSMNGQAAGY
   721  ELCGVLSRPS SKQNTPQYLA SPLDQEVVPC TPSHVGRPRL EKLSGLAAPD YTRLSPAKIV
   781  LRRHLSQDHT VPGRPAASEL HSRAEHTKEN GLPYQSPSVP GSMKLSPQDP RPLSPGALQL
   841  AGEKSSEKGL RERAYGSSGE LITSLPISIP LSTVQPNKLP VSIPLASVVL PSRAERARST
   901  PSPVLQPRDP SSTLEKQIGA NAHGAGSRSL ALAPAGFSYA GSVAISGALA GSPASLTPGA
   961  EPATLDESSS SGSLFATVGS RSSTPQHPLL LAQPRNSLPA SPAHQLSSSP RLGGAAQGPL
  1021  PEASKGDLPS DSGFSDPESE AKRRIVFTIT TGAGSAKQSP SSKHSPLTAS ARGDCVPSHG
  1081  QDSRRRGRRK RASAGTPSLS AGVSPKRRAL PSVAGLFTQP SGSPLNLNSM VSNINQPLEI
  1141  TAISSPETSL KSSPVPYQDH DQPPVLKKER PLSQTNGAHY SPLTSDEEPG SEDEPSSARI
  1201  ERKIATISLE SKSPPKTLEN GGGLAGRKPA PAGEPVNSSK WKSTFSPISD IGLAKSADSP
  1261  LQASSALSQN SLFTFRPALE EPSADAKLAA HPRKGFPGSL SGADGLSPGT NPANGCTFGG
  1321  GLAADLSLHS FSDGASLPHK GPEAAGLSSP LSFPSQRGKE GSDANPFLSK RQLDGLAGLK
  1381  GEGSRGKEAG EGGLPLCGPT DKTPLLSGKA AKARDREVDL KNGHNLFISA AAVPPGSLLS
  1441  GPGLAPAASS AGGAASSAQT HRSFLGPFPP GPQFALGPMS LQANLGSVAG SSVLQSLFSS
  1501  VPAAAGLVHV SSAATRLTNS HAMGSFSGVA GGTVGGN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DOT1L can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.59

Highest tissue expression

49 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DOT1L.

Disease | AllUniProt

Conditions DOT1L is implicated in, by any mechanism.

• Nil-Deshwar neurodevelopmental syndrome (NDNS) MIM:621265

Disease | GeneticClinVar

9 pathogenic / likely-pathogenic of 354 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Nil-Deshwar neurodevelopmental syndrome
• Inborn genetic diseases
• DOT1L-related condition
• Colon adenocarcinoma

Disease | ImmuneIEDB

Conditions an epitope on DOT1L was assayed in.

• glioblastoma T cell
• colonic benign neoplasm T cell
• type 1 diabetes mellitus T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.12

gnomAD pLI

1

gnomAD missense Z

2.72

DepMap mean gene effect

-0.17

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA damage checkpoint signaling
• DNA repair
• gene expression
• methylation
• positive regulation of transcription by RNA polymerase II
• regulation of receptor signaling pathway via JAK-STAT
• regulation of transcription regulatory region DNA binding
• sodium ion transport
• subtelomeric heterochromatin formation
• telomere organization

Molecular functions

• DNA binding
• histone H3 methyltransferase activity
• histone methyltransferase activity
• nucleic acid binding
• RNA polymerase II-specific DNA-binding transcription factor binding
• transcription coactivator activity
• histone H3K79 methyltransferase activity
• histone H3K79 trimethyltransferase activity

Cellular components

• chromosome, telomeric region
• cytoplasm
• nucleoplasm
• nucleus
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• S-adenosyl-L-methionine-dependent methyltransferase superfamily
• Histone H3-K79 methyltransferase, metazoa
• Histone-lysine N-methyltransferase DOT1 domain
• Histone H3-K79 methyltransferase
• Histone methylation protein DOT1

KeywordsUniProt

• Chromatin regulator
• DNA-binding
• Intellectual disability
• Methyltransferase
• Nucleus
• Phosphoprotein
• Repeat
• S-adenosyl-L-methionine
• Transferase

InteractionsUniProt · HPA

Protein binding partners of DOT1L in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MLLT10
• MLLT1
• MLLT3