Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q8TEK3 (DOT1L_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histone-lysine N-methyltransferase, H3 lysine-79 specific

EC=2.1.1.43
Alternative name(s):
DOT1-like protein
Histone H3-K79 methyltransferase
Short name=H3-K79-HMTase
Lysine N-methyltransferase 4
Gene names
Name:DOT1L
Synonyms:KIAA1814, KMT4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1739 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.

Catalytic activity

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. Ref.1

Subunit structure

Interacts with MLLT10. Ref.5 Ref.12

Subcellular location

Nucleus Ref.5.

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.

Sequence similarities

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

Contains 1 DOT1 domain.

Sequence caution

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

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MLLT1Q031114EBI-2619253,EBI-1384215

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: Q8TEK3-1)

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.
Isoform 1 (identifier: Q8TEK3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1537-1537: V → N
     1538-1739: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 17391739Histone-lysine N-methyltransferase, H3 lysine-79 specific
PRO_0000186089

Regions

Domain16 – 330315DOT1
Region136 – 1394S-adenosyl-L-methionine binding
Region159 – 16810S-adenosyl-L-methionine binding
Region222 – 2232S-adenosyl-L-methionine binding
Region391 – 41626Required for interaction with nucleosomes and DNA

Sites

Binding site1861S-adenosyl-L-methionine

Amino acid modifications

Modified residue3741Phosphoserine Ref.7 Ref.9 Ref.10 Ref.11
Modified residue4711Phosphoserine Ref.10
Modified residue4801Phosphothreonine Ref.10
Modified residue7751Phosphoserine Ref.7 Ref.10
Modified residue8341Phosphoserine Ref.10
Modified residue9001Phosphothreonine Ref.9
Modified residue9021Phosphoserine Ref.9 Ref.10 Ref.11
Modified residue10011Phosphoserine Ref.6 Ref.7 Ref.9 Ref.10
Modified residue10091Phosphoserine Ref.7
Modified residue10351Phosphoserine Ref.10
Modified residue12131Phosphoserine Ref.10

Natural variations

Alternative sequence15371V → N in isoform 1.
VSP_002228
Alternative sequence1538 – 1739202Missing in isoform 1.
VSP_002229
Natural variant7261L → M.
Corresponds to variant rs880525 [ dbSNP | Ensembl ].
VAR_014287
Natural variant13861G → S.
Corresponds to variant rs3815308 [ dbSNP | Ensembl ].
VAR_014288
Natural variant14181V → L.
Corresponds to variant rs2302061 [ dbSNP | Ensembl ].
VAR_014289

Experimental info

Mutagenesis163 – 1653GSG → RCR: Abolishes methyltransferase activity. Ref.1
Mutagenesis2411N → A or D: Loss of activity. Ref.12
Mutagenesis3121Y → A: Loss of activity. Ref.12
Mutagenesis3121Y → F: No effect. Ref.12
Sequence conflict2101G → E in BAB84946. Ref.4
Sequence conflict454 – 46714RSPHS…LPPSV → TLRTPSGSPRRTKL Ref.3
Sequence conflict4641P → L in BAB84946. Ref.4

Secondary structure

.............................................................. 1739
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 [UniParc].

Last modified November 15, 2002. Version 2.
Checksum: EBA575CE3C090CAC

FASTA1,739184,853
        10         20         30         40         50         60 
MGEKLELRLK SPVGAEPAVY PWPLPVYDKH HDAAHEIIET IRWVCEEIPD LKLAMENYVL 

        70         80         90        100        110        120 
IDYDTKSFES MQRLCDKYNR AIDSIHQLWK GTTQPMKLNT RPSTGLLRHI LQQVYNHSVT 

       130        140        150        160        170        180 
DPEKLNNYEP FSPEVYGETS FDLVAQMIDE IKMTDDDLFV DLGSGVGQVV LQVAAATNCK 

       190        200        210        220        230        240 
HHYGVEKADI PAKYAETMDR EFRKWMKWYG KKHAEYTLER GDFLSEEWRE RIANTSVIFV 

       250        260        270        280        290        300 
NNFAFGPEVD HQLKERFANM KEGGRIVSSK PFAPLNFRIN SRNLSDIGTI MRVVELSPLK 

       310        320        330        340        350        360 
GSVSWTGKPV SYYLHTIDRT ILENYFSSLK NPKLREEQEA ARRRQQRESK SNAATPTKGP 

       370        380        390        400        410        420 
EGKVAGPADA PMDSGAEEEK AGAATVKKPS PSKARKKKLN KKGRKMAGRK RGRPKKMNTA 

       430        440        450        460        470        480 
NPERKPKKNQ TALDALHAQT VSQTAASSPQ DAYRSPHSPF YQLPPSVQRH SPNPLLVAPT 

       490        500        510        520        530        540 
PPALQKLLES FKIQYLQFLA YTKTPQYKAS LQELLGQEKE KNAQLLGAAQ QLLSHCQAQK 

       550        560        570        580        590        600 
EEIRRLFQQK LDELGVKALT YNDLIQAQKE ISAHNQQLRE QSEQLEQDNR ALRGQSLQLL 

       610        620        630        640        650        660 
KARCEELQLD WATLSLEKLL KEKQALKSQI SEKQRHCLEL QISIVELEKS QRQQELLQLK 

       670        680        690        700        710        720 
SCVPPDDALS LHLRGKGALG RELEPDASRL HLELDCTKFS LPHLSSMSPE LSMNGQAAGY 

       730        740        750        760        770        780 
ELCGVLSRPS SKQNTPQYLA SPLDQEVVPC TPSHVGRPRL EKLSGLAAPD YTRLSPAKIV 

       790        800        810        820        830        840 
LRRHLSQDHT VPGRPAASEL HSRAEHTKEN GLPYQSPSVP GSMKLSPQDP RPLSPGALQL 

       850        860        870        880        890        900 
AGEKSSEKGL RERAYGSSGE LITSLPISIP LSTVQPNKLP VSIPLASVVL PSRAERARST 

       910        920        930        940        950        960 
PSPVLQPRDP SSTLEKQIGA NAHGAGSRSL ALAPAGFSYA GSVAISGALA GSPASLTPGA 

       970        980        990       1000       1010       1020 
EPATLDESSS SGSLFATVGS RSSTPQHPLL LAQPRNSLPA SPAHQLSSSP RLGGAAQGPL 

      1030       1040       1050       1060       1070       1080 
PEASKGDLPS DSGFSDPESE AKRRIVFTIT TGAGSAKQSP SSKHSPLTAS ARGDCVPSHG 

      1090       1100       1110       1120       1130       1140 
QDSRRRGRRK RASAGTPSLS AGVSPKRRAL PSVAGLFTQP SGSPLNLNSM VSNINQPLEI 

      1150       1160       1170       1180       1190       1200 
TAISSPETSL KSSPVPYQDH DQPPVLKKER PLSQTNGAHY SPLTSDEEPG SEDEPSSARI 

      1210       1220       1230       1240       1250       1260 
ERKIATISLE SKSPPKTLEN GGGLAGRKPA PAGEPVNSSK WKSTFSPISD IGLAKSADSP 

      1270       1280       1290       1300       1310       1320 
LQASSALSQN SLFTFRPALE EPSADAKLAA HPRKGFPGSL SGADGLSPGT NPANGCTFGG 

      1330       1340       1350       1360       1370       1380 
GLAADLSLHS FSDGASLPHK GPEAAGLSSP LSFPSQRGKE GSDANPFLSK RQLDGLAGLK 

      1390       1400       1410       1420       1430       1440 
GEGSRGKEAG EGGLPLCGPT DKTPLLSGKA AKARDREVDL KNGHNLFISA AAVPPGSLLS 

      1450       1460       1470       1480       1490       1500 
GPGLAPAASS AGGAASSAQT HRSFLGPFPP GPQFALGPMS LQANLGSVAG SSVLQSLFSS 

      1510       1520       1530       1540       1550       1560 
VPAAAGLVHV SSAATRLTNS HAMGSFSGVA GGTVGGVVFN HAVPSASAHP FGARVGRGAA 

      1570       1580       1590       1600       1610       1620 
CGSATLGPSP LQAAASASAS SFQAPASVET RPPPPPPPPP PPLPPPAHLG RSPAGPPVLH 

      1630       1640       1650       1660       1670       1680 
APPPPNAALP PPPTLLASNP EPALLQSLAS LPPNQAFLPP TSAASLPPAN ASLSIKLTSL 

      1690       1700       1710       1720       1730 
PHKGARPSFT VHHQPLPRLA LAQAAPGIPQ ASATGPSAVW VSLGMPPPYA AHLSGVKPR 

« Hide

Isoform 1 [UniParc].

Checksum: 9CEA12850DC4ACB1
Show »

FASTA1,537164,856

References

« Hide 'large scale' references
[1]"Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain."
Feng Q., Wang H., Ng H.H., Erdjument-Bromage H., Tempst P., Struhl K., Zhang Y.
Curr. Biol. 12:1052-1058(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME ACTIVITY, MUTAGENESIS OF 163-GLY--GLY-165.
[2]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., 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.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., 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 S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., 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 T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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."
Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.
DNA Res. 8:85-95(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 454-1739 (ISOFORM 2).
Tissue: Brain.
[4]"Characterization of long cDNA clones from human adult spleen. II. The complete sequences of 81 cDNA clones."
Jikuya H., Takano J., Kikuno R., Hirosawa M., Nagase T., Nomura N., Ohara O.
DNA Res. 10:49-57(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Spleen.
[5]"hDOT1L links histone methylation to leukemogenesis."
Okada Y., Feng Q., Lin Y., Jiang Q., Li Y., Coffield V.M., Su L., Xu G., Zhang Y.
Cell 121:167-178(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MLLT10, SUBCELLULAR LOCATION.
[6]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1001, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-374; SER-775; SER-1001 AND SER-1009, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-374; THR-900; SER-902 AND SER-1001, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-374; SER-471; THR-480; SER-775; SER-834; SER-902; SER-1001; SER-1035 AND SER-1213, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-374 AND SER-902, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase."
Min J., Feng Q., Li Z., Zhang Y., Xu R.-M.
Cell 112:711-723(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-416 IN COMPLEX WITH S-ADENOSINE-L-METHIONINE, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF ASN-241 AND TYR-312, NUCLEOSOME BINDING, INTERACTION WITH DNA.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF509504 mRNA. Translation: AAM88322.1.
AC004490 Genomic DNA. Translation: AAC08316.1. Sequence problems.
AB058717 mRNA. Translation: BAB47443.1.
AK074120 mRNA. Translation: BAB84946.1.
RefSeqNP_115871.1. NM_032482.2.
UniGeneHs.713641.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1NW3X-ray2.50A1-416[»]
3QOWX-ray2.10A1-416[»]
3QOXX-ray2.30A1-416[»]
3SR4X-ray2.50A1-351[»]
3SX0X-ray2.28A1-420[»]
3UWPX-ray2.05A1-420[»]
4EK9X-ray2.50A1-416[»]
4EKGX-ray2.80A1-416[»]
4EKIX-ray2.85A1-416[»]
4EQZX-ray2.15A1-420[»]
4ER0X-ray2.50A1-420[»]
4ER3X-ray2.40A1-351[»]
4ER5X-ray2.57A1-412[»]
4ER6X-ray2.30A1-412[»]
4ER7X-ray2.20A1-420[»]
4HRAX-ray3.15A1-416[»]
ProteinModelPortalQ8TEK3.
SMRQ8TEK3. Positions 4-344.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124082. 27 interactions.
DIPDIP-56410N.
IntActQ8TEK3. 3 interactions.
MINTMINT-6611327.
STRING9606.ENSP00000381657.

Chemistry

ChEMBLCHEMBL1795117.

PTM databases

PhosphoSiteQ8TEK3.

Polymorphism databases

DMDM25090171.

Proteomic databases

PaxDbQ8TEK3.
PRIDEQ8TEK3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000398665; ENSP00000381657; ENSG00000104885. [Q8TEK3-2]
GeneID84444.
KEGGhsa:84444.
UCSCuc002lvb.4. human. [Q8TEK3-2]
uc002lvc.1. human. [Q8TEK3-1]

Organism-specific databases

CTD84444.
GeneCardsGC19P002115.
HGNCHGNC:24948. DOT1L.
MIM607375. gene.
neXtProtNX_Q8TEK3.
PharmGKBPA134993717.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG294902.
HOGENOMHOG000143530.
HOVERGENHBG051393.
InParanoidQ8TEK3.
KOK11427.
OrthoDBEOG7W6WJV.
PhylomeDBQ8TEK3.
TreeFamTF106393.

Gene expression databases

ArrayExpressQ8TEK3.
BgeeQ8TEK3.
CleanExHS_DOT1L.
GenevestigatorQ8TEK3.

Family and domain databases

InterProIPR017956. AT_hook_DNA-bd_motif.
IPR013110. DOT1.
IPR025789. Histone_H3-K79_MeTrfase.
IPR021169. Histone_H3-K79_MeTrfase_met.
[Graphical view]
PfamPF08123. DOT1. 1 hit.
[Graphical view]
PIRSFPIRSF037123. Histone_H3-K79_MeTrfase_met. 1 hit.
SMARTSM00384. AT_hook. 1 hit.
[Graphical view]
PROSITEPS51569. DOT1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDOT1L. human.
EvolutionaryTraceQ8TEK3.
GeneWikiDOT1L.
GenomeRNAi84444.
NextBio74205.
PROQ8TEK3.
SOURCESearch...

Entry information

Entry nameDOT1L_HUMAN
AccessionPrimary (citable) accession number: Q8TEK3
Secondary accession number(s): O60379, Q96JL1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: November 15, 2002
Last modified: April 16, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM