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Protein

Histone-lysine N-methyltransferase, H3 lysine-79 specific

Gene

DOT1

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Histone methyltransferase that specifically methylates histone H3 to form H3K79me. This methylation is required for telomere silencing and for the pachytene checkpoint during the meiotic cell cycle by allowing the recruitment of RAD9 to double strand breaks. Nucleosomes are preferred as substrate compared to free histones. Can bind to DNA (in vitro).8 Publications

Catalytic activityi

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].PROSITE-ProRule annotation3 Publications

Enzyme regulationi

Ubiquitination of histone H2B by the RAD6/UBC2-BRE1 complex to form H2BK123ub1 is required for efficient DOT1 methyltransferase activity on histone H3. Interaction with DNA is required for optimal histone methyltransferase activity.2 Publications

pH dependencei

Optimum pH is 8 to 9.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei422S-adenosyl-L-methionine1

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • histone methyltransferase activity (H3-K79 specific) Source: SGD
  • nucleosomal histone binding Source: SGD

GO - Biological processi

  • chromatin silencing at telomere Source: SGD
  • DNA damage checkpoint Source: SGD
  • G1 DNA damage checkpoint Source: SGD
  • global genome nucleotide-excision repair Source: SGD
  • histone H3-K79 methylation Source: SGD
  • intra-S DNA damage checkpoint Source: SGD
  • meiotic recombination checkpoint Source: SGD
  • nucleotide-excision repair Source: SGD
  • postreplication repair Source: SGD
  • recombinational repair Source: SGD
  • regulation of transcription regulatory region DNA binding Source: GO_Central
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Transferase

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, S-adenosyl-L-methionine

Enzyme and pathway databases

BioCyciYEAST:G3O-29974-MONOMER.
ReactomeiR-SCE-3214841. PKMTs methylate histone lysines.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone-lysine N-methyltransferase, H3 lysine-79 specific (EC:2.1.1.43)
Alternative name(s):
Disrupter of telomere silencing protein 1
Histone H3-K79 methyltransferase
Short name:
H3-K79-HMTase
Lysine N-methyltransferase 4
Gene namesi
Name:DOT1
Synonyms:KMT4, PCH1
Ordered Locus Names:YDR440W
ORF Names:D9461.26
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome IV

Organism-specific databases

EuPathDBiFungiDB:YDR440W.
SGDiS000002848. DOT1.

Subcellular locationi

GO - Cellular componenti

  • chromosome, telomeric region Source: GOC
  • nucleus Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi301D → A or N: Abolishes methyltransferase activity. 1 Publication1
Mutagenesisi350Y → F: Reduces methyltransferase activity. 1 Publication1
Mutagenesisi372Y → F: Reduces methyltransferase activity. 1 Publication1
Mutagenesisi374E → A or Q: Abolishes methyltransferase activity. 1 Publication1
Mutagenesisi399G → R: Abolishes methyltransferase activity. 1 Publication1
Mutagenesisi401 – 403Missing : Abolishes methyltransferase activity. 1 Publication3
Mutagenesisi401G → A or R: Abolishes silencing function. 1 Publication1
Mutagenesisi422E → A: Abolishes S-adenosyl-L-methionine binding and methyltransferase activity. 1 Publication1
Mutagenesisi422E → D: No effect. 1 Publication1
Mutagenesisi543W → A: Abolishes methyltransferase activity, but not S-adenosyl-L-methionine binding. 1 Publication1
Mutagenesisi550Y → A: Abolishes methyltransferase activity, but not S-adenosyl-L-methionine binding. 1 Publication1
Mutagenesisi550Y → F: No effect. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001860911 – 582Histone-lysine N-methyltransferase, H3 lysine-79 specificAdd BLAST582

Proteomic databases

MaxQBiQ04089.
PRIDEiQ04089.

PTM databases

iPTMnetiQ04089.

Interactioni

GO - Molecular functioni

  • nucleosomal histone binding Source: SGD

Protein-protein interaction databases

BioGridi32496. 167 interactors.
DIPiDIP-2560N.
IntActiQ04089. 4 interactors.
MINTiMINT-426373.

Structurei

Secondary structure

1582
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi178 – 180Combined sources3
Beta strandi186 – 188Combined sources3
Helixi196 – 201Combined sources6
Helixi212 – 214Combined sources3
Beta strandi236 – 240Combined sources5
Beta strandi248 – 252Combined sources5
Beta strandi255 – 257Combined sources3
Beta strandi260 – 262Combined sources3
Helixi264 – 277Combined sources14
Helixi284 – 291Combined sources8
Helixi293 – 301Combined sources9
Helixi305 – 319Combined sources15
Helixi324 – 331Combined sources8
Beta strandi336 – 338Combined sources3
Helixi340 – 353Combined sources14
Helixi355 – 361Combined sources7
Helixi368 – 370Combined sources3
Helixi377 – 386Combined sources10
Beta strandi394 – 399Combined sources6
Helixi404 – 413Combined sources10
Beta strandi416 – 422Combined sources7
Helixi425 – 444Combined sources20
Beta strandi452 – 458Combined sources7
Helixi464 – 469Combined sources6
Helixi470 – 472Combined sources3
Beta strandi474 – 478Combined sources5
Helixi485 – 495Combined sources11
Beta strandi503 – 508Combined sources6
Beta strandi519 – 521Combined sources3
Helixi525 – 528Combined sources4
Beta strandi529 – 535Combined sources7
Beta strandi544 – 546Combined sources3
Beta strandi549 – 555Combined sources7
Helixi561 – 563Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1M0Rmodel-A392-511[»]
1U2ZX-ray2.20A/B/C158-582[»]
ProteinModelPortaliQ04089.
SMRiQ04089.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ04089.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini254 – 568DOT1PROSITE-ProRule annotationAdd BLAST315

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni158 – 172Required for interaction with nucleosomes and DNAAdd BLAST15
Regioni372 – 375S-adenosyl-L-methionine binding4
Regioni395 – 404S-adenosyl-L-methionine binding10
Regioni459 – 460S-adenosyl-L-methionine binding2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi106 – 169Lys-richAdd BLAST64

Sequence similaritiesi

Belongs to the class I-like SAM-binding methyltransferase superfamily. DOT1 family.PROSITE-ProRule annotation
Contains 1 DOT1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

GeneTreeiENSGT00390000013515.
HOGENOMiHOG000112251.
InParanoidiQ04089.
KOiK11427.
OMAiGEYYIST.
OrthoDBiEOG092C18VU.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR021162. Dot1.
IPR025789. DOT1_dom.
IPR030445. H3-K79_meTrfase.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR21451. PTHR21451. 1 hit.
PfamiPF08123. DOT1. 1 hit.
[Graphical view]
PIRSFiPIRSF017570. Histone_H3-K79_MeTrfase. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51569. DOT1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q04089-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGGQESISNN NSDSFIMSSP NLDSQESSIS PIDEKKGTDM QTKSLSSYSK
60 70 80 90 100
GTLLSKQVQN LLEEANKYDP IYGSSLPRGF LRDRNTKGKD NGLVPLVEKV
110 120 130 140 150
IPPIHKKTNN RNTRKKSSTT TKKDVKKPKA AKVKGKNGRT NHKHTPISKQ
160 170 180 190 200
EIDTAREKKP LKKGRANKKN DRDSPSSTFV DWNGPCLRLQ YPLFDIEYLR
210 220 230 240 250
SHEIYSGTPI QSISLRTNSP QPTSLTSDND TSSVTTAKLQ SILFSNYMEE
260 270 280 290 300
YKVDFKRSTA IYNPMSEIGK LIEYSCLVFL PSPYAEQLKE TILPDLNASF
310 320 330 340 350
DNSDTKGFVN AINLYNKMIR EIPRQRIIDH LETIDKIPRS FIHDFLHIVY
360 370 380 390 400
TRSIHPQANK LKHYKAFSNY VYGELLPNFL SDVYQQCQLK KGDTFMDLGS
410 420 430 440 450
GVGNCVVQAA LECGCALSFG CEIMDDASDL TILQYEELKK RCKLYGMRLN
460 470 480 490 500
NVEFSLKKSF VDNNRVAELI PQCDVILVNN FLFDEDLNKK VEKILQTAKV
510 520 530 540 550
GCKIISLKSL RSLTYQINFY NVENIFNRLK VQRYDLKEDS VSWTHSGGEY
560 570 580
YISTVMEDVD ESLFSPAARG RRNRGTPVKY TR
Length:582
Mass (Da):66,201
Last modified:November 1, 1996 - v1
Checksum:i05CAA6A8F8CBAB9A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U33007 Genomic DNA. Translation: AAB64868.1.
BK006938 Genomic DNA. Translation: DAA12277.1.
PIRiS69720.
RefSeqiNP_010728.1. NM_001180748.1.

Genome annotation databases

EnsemblFungiiYDR440W; YDR440W; YDR440W.
GeneIDi852050.
KEGGisce:YDR440W.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U33007 Genomic DNA. Translation: AAB64868.1.
BK006938 Genomic DNA. Translation: DAA12277.1.
PIRiS69720.
RefSeqiNP_010728.1. NM_001180748.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1M0Rmodel-A392-511[»]
1U2ZX-ray2.20A/B/C158-582[»]
ProteinModelPortaliQ04089.
SMRiQ04089.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi32496. 167 interactors.
DIPiDIP-2560N.
IntActiQ04089. 4 interactors.
MINTiMINT-426373.

PTM databases

iPTMnetiQ04089.

Proteomic databases

MaxQBiQ04089.
PRIDEiQ04089.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYDR440W; YDR440W; YDR440W.
GeneIDi852050.
KEGGisce:YDR440W.

Organism-specific databases

EuPathDBiFungiDB:YDR440W.
SGDiS000002848. DOT1.

Phylogenomic databases

GeneTreeiENSGT00390000013515.
HOGENOMiHOG000112251.
InParanoidiQ04089.
KOiK11427.
OMAiGEYYIST.
OrthoDBiEOG092C18VU.

Enzyme and pathway databases

BioCyciYEAST:G3O-29974-MONOMER.
ReactomeiR-SCE-3214841. PKMTs methylate histone lysines.

Miscellaneous databases

EvolutionaryTraceiQ04089.
PROiQ04089.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR021162. Dot1.
IPR025789. DOT1_dom.
IPR030445. H3-K79_meTrfase.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR21451. PTHR21451. 1 hit.
PfamiPF08123. DOT1. 1 hit.
[Graphical view]
PIRSFiPIRSF017570. Histone_H3-K79_MeTrfase. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51569. DOT1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDOT1_YEAST
AccessioniPrimary (citable) accession number: Q04089
Secondary accession number(s): D6VT67
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2002
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 152 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

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.
Present with 2160 molecules/cell in log phase SD medium.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome IV
    Yeast (Saccharomyces cerevisiae) chromosome IV: entries and gene names

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.