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Q04089 (DOT1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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):
Disrupter of telomere silencing protein 1
Histone H3-K79 methyltransferase
Short name=H3-K79-HMTase
Lysine N-methyltransferase 4
Gene names
Name:DOT1
Synonyms:KMT4, PCH1
Ordered Locus Names:YDR440W
ORF Names:D9461.26
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length582 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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). Ref.1 Ref.4 Ref.7 Ref.9 Ref.11 Ref.12 Ref.13 Ref.16

Catalytic activity

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. Ref.5 Ref.6 Ref.16

Enzyme regulation

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. Ref.8 Ref.16

Subcellular location

Nucleus Ref.4.

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.

Sequence similarities

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

Contains 1 DOT1 domain.

Biophysicochemical properties

pH dependence:

Optimum pH is 8 to 9. Ref.16

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   DomainRepeat
   LigandDNA-binding
S-adenosyl-L-methionine
   Molecular functionChromatin regulator
Methyltransferase
Transferase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage checkpoint

Inferred from mutant phenotype PubMed 17267293. Source: SGD

G1 DNA damage checkpoint

Inferred from mutant phenotype Ref.13. Source: SGD

chromatin silencing at telomere

Inferred from mutant phenotype Ref.4. Source: SGD

global genome nucleotide-excision repair

Inferred from mutant phenotype PubMed 21460225. Source: SGD

histone H3-K79 methylation

Inferred from direct assay Ref.6. Source: SGD

intra-S DNA damage checkpoint

Inferred from mutant phenotype Ref.13. Source: SGD

meiotic recombination checkpoint

Inferred from genetic interaction Ref.4. Source: SGD

nucleotide-excision repair

Inferred from mutant phenotype PubMed 17267293. Source: SGD

postreplication repair

Inferred from genetic interaction PubMed 17267293. Source: SGD

recombinational repair

Inferred from mutant phenotype PubMed 17267293. Source: SGD

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from direct assay Ref.4. Source: SGD

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

histone methyltransferase activity (H3-K79 specific)

Inferred from direct assay Ref.6PubMed 18158898. Source: SGD

nucleosomal histone binding

Inferred from direct assay PubMed 18158898. Source: SGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 582582Histone-lysine N-methyltransferase, H3 lysine-79 specific
PRO_0000186091

Regions

Domain254 – 568315DOT1
Region158 – 17215Required for interaction with nucleosomes and DNA
Region372 – 3754S-adenosyl-L-methionine binding
Region395 – 40410S-adenosyl-L-methionine binding
Region459 – 4602S-adenosyl-L-methionine binding
Compositional bias106 – 16964Lys-rich

Sites

Binding site4221S-adenosyl-L-methionine

Experimental info

Mutagenesis3011D → A or N: Abolishes methyltransferase activity. Ref.16
Mutagenesis3501Y → F: Reduces methyltransferase activity. Ref.16
Mutagenesis3721Y → F: Reduces methyltransferase activity. Ref.16
Mutagenesis3741E → A or Q: Abolishes methyltransferase activity. Ref.16
Mutagenesis3991G → R: Abolishes methyltransferase activity. Ref.6
Mutagenesis401 – 4033Missing: Abolishes methyltransferase activity. Ref.5 Ref.6
Mutagenesis4011G → A or R: Abolishes silencing function. Ref.5
Mutagenesis4221E → A: Abolishes S-adenosyl-L-methionine binding and methyltransferase activity. Ref.16
Mutagenesis4221E → D: No effect. Ref.16
Mutagenesis5431W → A: Abolishes methyltransferase activity, but not S-adenosyl-L-methionine binding. Ref.16
Mutagenesis5501Y → A: Abolishes methyltransferase activity, but not S-adenosyl-L-methionine binding. Ref.16
Mutagenesis5501Y → F: No effect. Ref.16

Secondary structure

................................................................... 582
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q04089 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 05CAA6A8F8CBAB9A

FASTA58266,201
        10         20         30         40         50         60 
MGGQESISNN NSDSFIMSSP NLDSQESSIS PIDEKKGTDM QTKSLSSYSK GTLLSKQVQN 

        70         80         90        100        110        120 
LLEEANKYDP IYGSSLPRGF LRDRNTKGKD NGLVPLVEKV IPPIHKKTNN RNTRKKSSTT 

       130        140        150        160        170        180 
TKKDVKKPKA AKVKGKNGRT NHKHTPISKQ EIDTAREKKP LKKGRANKKN DRDSPSSTFV 

       190        200        210        220        230        240 
DWNGPCLRLQ YPLFDIEYLR SHEIYSGTPI QSISLRTNSP QPTSLTSDND TSSVTTAKLQ 

       250        260        270        280        290        300 
SILFSNYMEE YKVDFKRSTA IYNPMSEIGK LIEYSCLVFL PSPYAEQLKE TILPDLNASF 

       310        320        330        340        350        360 
DNSDTKGFVN AINLYNKMIR EIPRQRIIDH LETIDKIPRS FIHDFLHIVY TRSIHPQANK 

       370        380        390        400        410        420 
LKHYKAFSNY VYGELLPNFL SDVYQQCQLK KGDTFMDLGS GVGNCVVQAA LECGCALSFG 

       430        440        450        460        470        480 
CEIMDDASDL TILQYEELKK RCKLYGMRLN NVEFSLKKSF VDNNRVAELI PQCDVILVNN 

       490        500        510        520        530        540 
FLFDEDLNKK VEKILQTAKV GCKIISLKSL RSLTYQINFY NVENIFNRLK VQRYDLKEDS 

       550        560        570        580 
VSWTHSGGEY YISTVMEDVD ESLFSPAARG RRNRGTPVKY TR 

« Hide

References

« Hide 'large scale' references
[1]"Identification of high-copy disruptors of telomeric silencing in Saccharomyces cerevisiae."
Singer M.S., Kahana A., Wolf A.J., Meisinger L.L., Peterson S.E., Goggin C., Mahowald M., Gottschling D.E.
Genetics 150:613-632(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION.
[2]"The nucleotide sequence of Saccharomyces cerevisiae chromosome IV."
Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G., Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C., Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F., Delaveau T. expand/collapse author list , del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M., Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T., Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C., Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S., Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L., Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H., Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M., Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M., Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A., Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G., Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E., Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S., Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D., Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V., Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E., Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M., Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X., Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A., Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T., Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L., Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E., Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L., Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M., Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K., Mewes H.-W., Zollner A., Zaccaria P.
Nature 387:75-78(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[3]"The reference genome sequence of Saccharomyces cerevisiae: Then and now."
Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.
G3 (Bethesda) 4:389-398(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION.
Strain: ATCC 204508 / S288c.
[4]"Role for the silencing protein Dot1 in meiotic checkpoint control."
San-Segundo P.A., Roeder G.S.
Mol. Biol. Cell 11:3601-3615(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[5]"Dot1p modulates silencing in yeast by methylation of the nucleosome core."
van Leeuwen F., Gafken P.R., Gottschling D.E.
Cell 109:745-756(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME ACTIVITY, MUTAGENESIS OF GLY-401.
[6]"Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association."
Ng H.H., Feng Q., Wang H., Erdjument-Bromage H., Tempst P., Zhang Y., Struhl K.
Genes Dev. 16:1518-1527(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME ACTIVITY, MUTAGENESIS OF GLY-399 AND 401-GLY--GLY-403.
[7]"Disruptor of telomeric silencing-1 is a chromatin-specific histone H3 methyltransferase."
Lacoste N., Utley R.T., Hunter J.M., Poirier G.G., Cote J.
J. Biol. Chem. 277:30421-30424(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone H3 lysine 79."
Ng H.H., Xu R.-M., Zhang Y., Struhl K.
J. Biol. Chem. 277:34655-34657(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[9]"Gene silencing: trans-histone regulatory pathway in chromatin."
Briggs S.D., Xiao T., Sun Z.-W., Caldwell J.A., Shabanowitz J., Hunt D.F., Allis C.D., Strahl B.D.
Nature 418:498-498(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Global analysis of protein expression in yeast."
Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S.
Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[11]"Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation."
Ng H.H., Ciccone D.N., Morshead K.B., Oettinger M.A., Struhl K.
Proc. Natl. Acad. Sci. U.S.A. 100:1820-1825(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1."
Giannattasio M., Lazzaro F., Plevani P., Muzi-Falconi M.
J. Biol. Chem. 280:9879-9886(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9."
Wysocki R., Javaheri A., Allard S., Sha F., Cote J., Kron S.J.
Mol. Cell. Biol. 25:8430-8443(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"A multidimensional chromatography technology for in-depth phosphoproteome analysis."
Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.
Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution."
Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.
Science 325:1682-1686(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Structure of the conserved core of the yeast Dot1p, a nucleosomal histone H3 lysine 79 methyltransferase."
Sawada K., Yang Z., Horton J.R., Collins R.E., Zhang X., Cheng X.
J. Biol. Chem. 279:43296-43306(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 158-582 IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE, CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, DNA-BINDING, MUTAGENESIS OF ASP-301; TYR-350; TYR-372; GLU-374; GLU-422; TRP-543 AND TYR-550.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U33007 Genomic DNA. Translation: AAB64868.1.
BK006938 Genomic DNA. Translation: DAA12277.1.
PIRS69720.
RefSeqNP_010728.1. NM_001180748.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M0Rmodel-A392-511[»]
1U2ZX-ray2.20A/B/C158-582[»]
ProteinModelPortalQ04089.
SMRQ04089. Positions 176-567.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid32496. 162 interactions.
DIPDIP-2560N.
IntActQ04089. 4 interactions.
MINTMINT-426373.
STRING4932.YDR440W.

Proteomic databases

MaxQBQ04089.
PaxDbQ04089.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYDR440W; YDR440W; YDR440W.
GeneID852050.
KEGGsce:YDR440W.

Organism-specific databases

CYGDYDR440w.
SGDS000002848. DOT1.

Phylogenomic databases

eggNOGNOG294902.
GeneTreeENSGT00390000013515.
HOGENOMHOG000112251.
KOK11427.
OMAYTRSIHP.
OrthoDBEOG7KH9VN.

Enzyme and pathway databases

BioCycYEAST:G3O-29974-MONOMER.

Gene expression databases

GenevestigatorQ04089.

Family and domain databases

Gene3D3.40.50.150. 1 hit.
InterProIPR013110. DOT1.
IPR025789. Histone_H3-K79_MeTrfase.
IPR021162. Histone_H3-K79_MeTrfase_fungi.
IPR029063. SAM-dependent_MTases-like.
[Graphical view]
PfamPF08123. DOT1. 1 hit.
[Graphical view]
PIRSFPIRSF017570. Histone_H3-K79_MeTrfase. 1 hit.
SUPFAMSSF53335. SSF53335. 1 hit.
PROSITEPS51569. DOT1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ04089.
NextBio970311.
PROQ04089.

Entry information

Entry nameDOT1_YEAST
AccessionPrimary (citable) accession number: Q04089
Secondary accession number(s): D6VT67
Entry history
Integrated into UniProtKB/Swiss-Prot: July 11, 2002
Last sequence update: November 1, 1996
Last modified: June 11, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome IV

Yeast (Saccharomyces cerevisiae) chromosome IV: entries and gene names

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references