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UniProtKB/Swiss-Prot entry Q8TEK3


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name DOT1L_HUMAN
Primary accession number Q8TEK3
Secondary accession numbers O60379 Q96JL1
Integrated into Swiss-Prot on November 15, 2002
Sequence was last modified on November 15, 2002 (Sequence version 2)
Annotations were last modified on    November 25, 2008 (Entry version 69)
Name and origin of the protein
Protein name Histone-lysine N-methyltransferase, H3 lysine-79 specific
Synonyms EC 2.1.1.43
Histone H3-K79 methyltransferase
H3-K79-HMTase
DOT1-like protein
Lysine N-methyltransferase 4
Gene name
Name: DOT1L
Synonyms: KIAA1814, KMT4
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME ACTIVITY, AND MUTAGENESIS OF 163-GLY--GLY-165.
DOI=10.1016/S0960-9822(02)00901-6; PubMed=12123582 [NCBI, ExPASy, EBI, Israel, Japan]
Feng Q., Wang H., Ng H.H., Erdjument-Bromage H., Tempst P., Struhl K., Zhang Y.;
"Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain.";
Curr. Biol. 12:1052-1058(2002).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature02399; PubMed=15057824 [NCBI, ExPASy, EBI, Israel, Japan]
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., 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.;
"The DNA sequence and biology of human chromosome 19.";
Nature 428:529-535(2004).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 454-1739 (ISOFORM 2).
TISSUE=Brain;
DOI=10.1093/dnares/8.2.85; PubMed=11347906 [NCBI, ExPASy, EBI, Israel, Japan]
Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
"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.";
DNA Res. 8:85-95(2001).
[4]
PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Spleen;
DOI=10.1093/dnares/10.1.49; PubMed=12693554 [NCBI, ExPASy, EBI, Israel, Japan]
Jikuya H., Takano J., Kikuno R., Hirosawa M., Nagase T., Nomura N., Ohara O.;
"Characterization of long cDNA clones from human adult spleen. II. The complete sequences of 81 cDNA clones.";
DNA Res. 10:49-57(2003).
[5]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-297, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1021/pr070152u; PubMed=17924679 [NCBI, ExPASy, EBI, Israel, Japan]
Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra.";
J. Proteome Res. 6:4150-4162(2007).
[6]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1001; SER-1009 AND SER-1349, AND MASS SPECTROMETRY.
DOI=10.1021/pr0705441; PubMed=18220336 [NCBI, ExPASy, EBI, Israel, Japan]
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.";
J. Proteome Res. 7:1346-1351(2008).
[7]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-374; SER-471; THR-480; SER-775; SER-822; SER-834; SER-899; THR-900; SER-902; SER-1001 AND SER-1009, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0805139105; PubMed=18669648 [NCBI, ExPASy, EBI, Israel, Japan]
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[8]
X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-416 IN COMPLEX WITH S-ADENOSINE-L-METHIONINE, MASS SPECTROMETRY, MUTAGENESIS OF ASN-241 AND TYR-312, NUCLEOSOME BINDING, AND INTERACTION WITH DNA.
DOI=10.1016/S0092-8674(03)00114-4; PubMed=12628190 [NCBI, ExPASy, EBI, Israel, Japan]
Min J., Feng Q., Li Z., Zhang Y., Xu R.-M.;
"Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase.";
Cell 112:711-723(2003).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AF509504; AAM88322.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC004490; AAC08316.1; ALT_SEQ; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB058717; BAB47443.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK074120; BAB84946.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_115871.1; -.
UniGene Hs.591379
3D structure databases
PDB
1NW3; X-ray; 2.50 A; A=1-416.[ExPASy / RCSB / EBI]
PDBsum 1NW3; -.
ModBase Q8TEK3.
PTM databases
PhosphoSite Q8TEK3; -.
Organism-specific databases
H-InvDB HIX0014609; -.
HGNC HGNC:24948; DOT1L.
GenAtlas DOT1L.
MIM 607375; gene. [NCBI / EBI]
PharmGKB PA134993717; -.
GeneCards Q8TEK3.
HUGE KIAA1814.
Gene expression databases
ArrayExpress Q8TEK3; -.
CleanEx HS_DOT1L; -.
GermOnline ENSG00000104885; Homo sapiens.
Ontologies
GO
GO:0005634; Cellular component: nucleus (inferred from electronic annotation from InterPro).
GO:0003677; Molecular function: DNA binding (inferred from electronic annotation from InterPro).
GO:0018024; Molecular function: histone-lysine N-methyltransferase activity (inferred from electronic annotation from InterPro).
GO:0016568; Biological process: chromatin modification (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.
Family and domain databases
InterPro IPR000637; AT_hook_DNA_bd.
IPR013110; DOT1.
Graphical view of domain structure.
Pfam PF02178; AT_hook; 1.
PF08123; DOT1; 1.
Pfam graphical view of domain structure.
SMART SM00384; AT_hook; 1.
SMART graphical view of domain structure.
ProtoNet Q8TEK3.
Genome annotation databases
Ensembl ENSG00000104885; Homo sapiens. [Contig view]
GeneID 84444; -.
KEGG hsa:84444; -.
Phylogenomic databases
HOGENOM Q8TEK3; -.
HOVERGEN Q8TEK3; -.
Other
NextBio 74205; -.
SOURCE DOT1L; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; Chromatin regulator; DNA-binding; Methyltransferase; Nucleus; Phosphoprotein; Polymorphism; Repeat; S-adenosyl-L-methionine; Transferase.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
CHAIN   1   1739  1739     Histone-lysine N-methyltransferase, H3 lysine-79 specific. PRO_0000186089
REGION   161    163  3     S-adenosyl-L-methionine binding. 
REGION   391    416  26     Required for interaction with nucleosomes and DNA. 
MOTIF   157    168  12     SAM-binding motif 1. 
MOTIF   183    189  7     SAM-binding motif 2. 
MOTIF   236    245  10     SAM-binding motif 3. 
BINDING   139    139        S-adenosyl-L-methionine. 
BINDING   168    168        S-adenosyl-L-methionine. 
BINDING   186    186        S-adenosyl-L-methionine. 
BINDING   222    222        S-adenosyl-L-methionine. 
MOD_RES   297    297        Phosphoserine. 
MOD_RES   374    374        Phosphoserine. 
MOD_RES   471    471        Phosphoserine. 
MOD_RES   480    480        Phosphothreonine. 
MOD_RES   775    775        Phosphoserine. 
MOD_RES   822    822        Phosphoserine. 
MOD_RES   834    834        Phosphoserine. 
MOD_RES   899    899        Phosphoserine. 
MOD_RES   900    900        Phosphothreonine. 
MOD_RES   902    902        Phosphoserine. 
MOD_RES   1001   1001        Phosphoserine. 
MOD_RES   1009   1009        Phosphoserine. 
MOD_RES   1349   1349        Phosphoserine. 
VAR_SEQ   1537   1537        V -> N (in isoform 1). VSP_002228
VAR_SEQ   1538   1739        Missing (in isoform 1). VSP_002229
VARIANT   726    726  1     L -> M (in dbSNP:rs880525 [NCBI]). VAR_014287 
VARIANT   1386   1386  1     G -> S (in dbSNP:rs3815308 [NCBI]). VAR_014288 
VARIANT   1418   1418  1     V -> L (in dbSNP:rs2302061 [NCBI]). VAR_014289 
MUTAGEN   163    165        GSG->RCR: Abolishes methyltransferase activity. 
MUTAGEN   241    241        N->A,D: Loss of activity. 
MUTAGEN   312    312        Y->A: Loss of activity. 
MUTAGEN   312    312        Y->F: No effect. 
CONFLICT   210    210        G -> E (in Ref. 4; BAB84946). 
CONFLICT   454    467        RSPHSPFYQLPPSV -> TLRTPSGSPRRTKL (in Ref. 3). 
CONFLICT   464    464        P -> L (in Ref. 4; BAB84946). 
STRAND   6      9  4      
STRAND   18     23  6      
STRAND   26     28  3      
HELIX   33     47  15      
HELIX   49     55  7      
STRAND   56     58  3      
HELIX   68     90  23      
HELIX   104    118  15      
HELIX   122    126  5      
STRAND   130    132  3      
HELIX   141    150  10      
STRAND   158    163  6      
HELIX   168    176  9      
STRAND   180    186  7      
HELIX   189    209  21      
STRAND   216    220  5      
HELIX   226    234  9      
STRAND   236    240  5      
TURN   243    245  3      
HELIX   247    257  11      
STRAND   265    270  6      
HELIX   287    290  4      
STRAND   291    295  5      
STRAND   307    309  3      
STRAND   313    317  5      
HELIX   320    330  11      
Sequence information
Length: 1739 AA [This is the length of the unprocessed precursor] Molecular weight: 184853 Da [This is the MW of the unprocessed precursor] CRC64: EBA575CE3C090CAC [This is a checksum on the sequence]
        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 

Q8TEK3 in FASTA format

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