Histone-lysine N-methyltransferase, H3 lysine-79 specific - Saccharomyces cerevisiae (Baker's yeast)

Names and origin

Protein names

Recommended name:
    Histone-lysine N-methyltransferase, H3 lysine-79 specific
    EC=2.1.1.43
Alternative name(s):
    Histone H3-K79 methyltransferase
      Short name=H3-K79-HMTase
    Disrupter of telomere silencing protein 1
    Lysine N-methyltransferase 4

Gene names

Name:	DOT1
Synonyms:	KMT4, PCH1
Ordered Locus Names:	YDR440W
ORF Names:	D9461.26

Organism

Saccharomyces cerevisiae (Baker's yeast) [Complete proteome]

Taxonomic identifier

4932 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

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Protein attributes

Sequence length	582 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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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.3 Ref.6 Ref.8 Ref.10 Ref.11 Ref.12 Ref.14
Catalytic activity	S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].
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.14 Ref.7
Subcellular location	Nucleus Ref.3.
Miscellaneous	In contrast to other lysine histone methyltransferase, 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. Ref.9
Sequence similarities	Belongs to the DOT1 family.
Biophysicochemical properties	pH dependence: Optimum pH is 8 to 9.

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Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Repeat
Ligand	DNA-binding S-adenosyl-L-methionine
Molecular function	Chromatin regulator Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	DNA damage checkpoint Inferred from genetic interaction. Source: SGD chromatin silencing at telomere Ref.3 Inferred from mutant phenotype. Source: SGD histone H3-K79 methylation Ref.5 Inferred from direct assay. Source: SGD meiotic recombination checkpoint Ref.3 Inferred from genetic interaction. Source: SGD nucleotide-excision repair Inferred from genetic interaction. Source: SGD postreplication repair Inferred from genetic interaction. Source: SGD recombinational repair Inferred from genetic interaction. Source: SGD transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Ref.3 Inferred from direct assay. Source: SGD
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW histone methyltransferase activity (H3-K79 specific) Ref.5 Inferred from direct assay. Source: SGD nucleosomal histone binding Inferred from direct assay. Source: SGD
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
SWD2	P36104	1	EBI-6046,EBI-26608

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 582

582

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

PRO_0000186091

Regions

Region

158 – 172

15

Required for interaction with nucleosomes and DNA

Region

397 – 399

3

S-adenosyl-L-methionine binding

Region

459 – 460

2

S-adenosyl-L-methionine binding

Motif

393 – 404

12

SAM-binding motif 1

Motif

474 – 483

10

SAM-binding motif 2

Compositional bias

106 – 169

64

Lys-rich

Sites

Binding site

375

1

S-adenosyl-L-methionine; via amide nitrogen

Binding site

422

1

S-adenosyl-L-methionine

Amino acid modifications

Modified residue

219

1

Phosphoserine Ref.13

Experimental info

Mutagenesis

301

1

D → A or N: Abolishes methyltransferase activity. Ref.14

Mutagenesis

350

1

Y → F: Reduces methyltransferase activity. Ref.14

Mutagenesis

372

1

Y → F: Reduces methyltransferase activity. Ref.14

Mutagenesis

374

1

E → A or Q: Abolishes methyltransferase activity. Ref.14

Mutagenesis

399

1

G → R: Abolishes methyltransferase activity. Ref.5

Mutagenesis

401 – 403

3

Missing: Abolishes methyltransferase activity. Ref.4 Ref.5

Mutagenesis

401

1

G → A or R: Abolishes silencing function. Ref.4

Mutagenesis

422

1

E → A: Abolishes S-adenosyl-L-methionine binding and methyltransferase activity. Ref.14

Mutagenesis

422

1

E → D: No effect. Ref.14

Mutagenesis

543

1

W → A: Abolishes methyltransferase activity, but not S-adenosyl-L-methionine binding. Ref.14

Mutagenesis

550

1

Y → A: Abolishes methyltransferase activity, but not S-adenosyl-L-methionine binding. Ref.14

Mutagenesis

550

1

Y → F: No effect. Ref.14

Secondary structure

1

.

582

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

Q04089-1 [UniParc].

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

582

66,201

        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

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References

	« Hide 'large scale' referencesShow '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: 9755194] [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. Zaccaria P. Nature 387:75-78(1997) [PubMed: 9169867] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[3]	"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: 11029058] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[4]	"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: 12086673] [Abstract] Cited for: ENZYME ACTIVITY, MUTAGENESIS OF GLY-401.
[5]	"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: 12080090] [Abstract] Cited for: ENZYME ACTIVITY, MUTAGENESIS OF GLY-399 AND 401-GLY--GLY-403.
[6]	"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: 12097318] [Abstract] Cited for: FUNCTION.
[7]	"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: 12167634] [Abstract] Cited for: ENZYME REGULATION.
[8]	"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: 12152067] [Abstract] Cited for: FUNCTION.
[9]	"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: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[10]	"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: 12574507] [Abstract] Cited for: FUNCTION.
[11]	"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: 15632126] [Abstract] Cited for: FUNCTION.
[12]	"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: 16166626] [Abstract] Cited for: FUNCTION.
[13]	"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: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, MASS SPECTROMETRY.
[14]	"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: 15292170] [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.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U33007 Genomic DNA. Translation: AAB64868.1.

PIR

S69720.

RefSeq

NP_010728.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M0R	model	-	A	392-511	[»]
1U2Z	X-ray	2.20	A/B/C	158-582	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-2560N.

IntAct

Q04089. 2 interactions.

STRING

Q04089.

Genome annotation databases

Ensembl

YDR440W; YDR440W; YDR440W; Saccharomyces cerevisiae. [Genome view]

GeneID

852050.

KEGG

sce:YDR440W.

NMPDR

fig|4932.3.peg.1501.

Organism-specific databases

CYGD

YDR440w.

SGD

S000002848. DOT1.

Phylogenomic databases

eggNOG

HOGENOM

OMA

OrthoDB

PhylomeDB

Q04089.

Enzyme and pathway databases

BRENDA

2.1.1.43. 250.

Gene expression databases

ArrayExpress

Q04089.

Genevestigator

Q04089.

GermOnline

YDR440W. Saccharomyces cerevisiae.

Family and domain databases

ProtoNet

Search...

Other Resources

NextBio

970311.

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Entry information

Entry name

DOT1_YEAST

Accession

Primary (citable) accession number: Q04089

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2002
Last sequence update:	November 1, 1996
Last modified:	February 9, 2010
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)

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Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Yeast

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

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents