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Q04089

- DOT1_YEAST

UniProt

Q04089 - DOT1_YEAST

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: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 132 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    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].3 PublicationsPROSITE-ProRule annotation

    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)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei422 – 4221S-adenosyl-L-methionine

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB-KW
    2. histone methyltransferase activity (H3-K79 specific) Source: SGD
    3. nucleosomal histone binding Source: SGD

    GO - Biological processi

    1. chromatin silencing at telomere Source: SGD
    2. DNA damage checkpoint Source: SGD
    3. G1 DNA damage checkpoint Source: SGD
    4. global genome nucleotide-excision repair Source: SGD
    5. histone H3-K79 methylation Source: SGD
    6. intra-S DNA damage checkpoint Source: SGD
    7. meiotic recombination checkpoint Source: SGD
    8. nucleotide-excision repair Source: SGD
    9. postreplication repair Source: SGD
    10. recombinational repair Source: SGD
    11. transcription, DNA-templated Source: UniProtKB-KW

    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.

    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
    ProteomesiUP000002311: Chromosome IV

    Organism-specific databases

    CYGDiYDR440w.
    SGDiS000002848. DOT1.

    Subcellular locationi

    Nucleus 1 Publication

    GO - Cellular componenti

    1. nucleus Source: SGD

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi301 – 3011D → A or N: Abolishes methyltransferase activity. 1 Publication
    Mutagenesisi350 – 3501Y → F: Reduces methyltransferase activity. 1 Publication
    Mutagenesisi372 – 3721Y → F: Reduces methyltransferase activity. 1 Publication
    Mutagenesisi374 – 3741E → A or Q: Abolishes methyltransferase activity. 1 Publication
    Mutagenesisi399 – 3991G → R: Abolishes methyltransferase activity. 1 Publication
    Mutagenesisi401 – 4033Missing: Abolishes methyltransferase activity. 1 Publication
    Mutagenesisi401 – 4011G → A or R: Abolishes silencing function. 1 Publication
    Mutagenesisi422 – 4221E → A: Abolishes S-adenosyl-L-methionine binding and methyltransferase activity. 1 Publication
    Mutagenesisi422 – 4221E → D: No effect. 1 Publication
    Mutagenesisi543 – 5431W → A: Abolishes methyltransferase activity, but not S-adenosyl-L-methionine binding. 1 Publication
    Mutagenesisi550 – 5501Y → A: Abolishes methyltransferase activity, but not S-adenosyl-L-methionine binding. 1 Publication
    Mutagenesisi550 – 5501Y → F: No effect. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 582582Histone-lysine N-methyltransferase, H3 lysine-79 specificPRO_0000186091Add
    BLAST

    Proteomic databases

    MaxQBiQ04089.
    PaxDbiQ04089.

    Expressioni

    Gene expression databases

    GenevestigatoriQ04089.

    Interactioni

    Protein-protein interaction databases

    BioGridi32496. 163 interactions.
    DIPiDIP-2560N.
    IntActiQ04089. 4 interactions.
    MINTiMINT-426373.
    STRINGi4932.YDR440W.

    Structurei

    Secondary structure

    1
    582
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi178 – 1803
    Beta strandi186 – 1883
    Helixi196 – 2016
    Helixi212 – 2143
    Beta strandi236 – 2405
    Beta strandi248 – 2525
    Beta strandi255 – 2573
    Beta strandi260 – 2623
    Helixi264 – 27714
    Helixi284 – 2918
    Helixi293 – 3019
    Helixi305 – 31915
    Helixi324 – 3318
    Beta strandi336 – 3383
    Helixi340 – 35314
    Helixi355 – 3617
    Helixi368 – 3703
    Helixi377 – 38610
    Beta strandi394 – 3996
    Helixi404 – 41310
    Beta strandi416 – 4227
    Helixi425 – 44420
    Beta strandi452 – 4587
    Helixi464 – 4696
    Helixi470 – 4723
    Beta strandi474 – 4785
    Helixi485 – 49511
    Beta strandi503 – 5086
    Beta strandi519 – 5213
    Helixi525 – 5284
    Beta strandi529 – 5357
    Beta strandi544 – 5463
    Beta strandi549 – 5557
    Helixi561 – 5633

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1M0Rmodel-A392-511[»]
    1U2ZX-ray2.20A/B/C158-582[»]
    ProteinModelPortaliQ04089.
    SMRiQ04089. Positions 176-567.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ04089.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini254 – 568315DOT1PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni158 – 17215Required for interaction with nucleosomes and DNAAdd
    BLAST
    Regioni372 – 3754S-adenosyl-L-methionine binding
    Regioni395 – 40410S-adenosyl-L-methionine binding
    Regioni459 – 4602S-adenosyl-L-methionine binding

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi106 – 16964Lys-richAdd
    BLAST

    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

    eggNOGiNOG294902.
    GeneTreeiENSGT00390000013515.
    HOGENOMiHOG000112251.
    KOiK11427.
    OMAiYTRSIHP.
    OrthoDBiEOG7KH9VN.

    Family and domain databases

    Gene3Di3.40.50.150. 1 hit.
    InterProiIPR013110. DOT1.
    IPR025789. Histone_H3-K79_MeTrfase.
    IPR021162. Histone_H3-K79_MeTrfase_fungi.
    IPR029063. SAM-dependent_MTases-like.
    [Graphical view]
    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

    MGGQESISNN NSDSFIMSSP NLDSQESSIS PIDEKKGTDM QTKSLSSYSK    50
    GTLLSKQVQN LLEEANKYDP IYGSSLPRGF LRDRNTKGKD NGLVPLVEKV 100
    IPPIHKKTNN RNTRKKSSTT TKKDVKKPKA AKVKGKNGRT NHKHTPISKQ 150
    EIDTAREKKP LKKGRANKKN DRDSPSSTFV DWNGPCLRLQ YPLFDIEYLR 200
    SHEIYSGTPI QSISLRTNSP QPTSLTSDND TSSVTTAKLQ SILFSNYMEE 250
    YKVDFKRSTA IYNPMSEIGK LIEYSCLVFL PSPYAEQLKE TILPDLNASF 300
    DNSDTKGFVN AINLYNKMIR EIPRQRIIDH LETIDKIPRS FIHDFLHIVY 350
    TRSIHPQANK LKHYKAFSNY VYGELLPNFL SDVYQQCQLK KGDTFMDLGS 400
    GVGNCVVQAA LECGCALSFG CEIMDDASDL TILQYEELKK RCKLYGMRLN 450
    NVEFSLKKSF VDNNRVAELI PQCDVILVNN FLFDEDLNKK VEKILQTAKV 500
    GCKIISLKSL RSLTYQINFY NVENIFNRLK VQRYDLKEDS VSWTHSGGEY 550
    YISTVMEDVD ESLFSPAARG RRNRGTPVKY TR 582
    Length:582
    Mass (Da):66,201
    Last modified:November 1, 1996 - v1
    Checksum:i05CAA6A8F8CBAB9A
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U33007 Genomic DNA. Translation: AAB64868.1 .
    BK006938 Genomic DNA. Translation: DAA12277.1 .
    PIRi S69720.
    RefSeqi NP_010728.1. NM_001180748.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1M0R model - A 392-511 [» ]
    1U2Z X-ray 2.20 A/B/C 158-582 [» ]
    ProteinModelPortali Q04089.
    SMRi Q04089. Positions 176-567.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 32496. 163 interactions.
    DIPi DIP-2560N.
    IntActi Q04089. 4 interactions.
    MINTi MINT-426373.
    STRINGi 4932.YDR440W.

    Proteomic databases

    MaxQBi Q04089.
    PaxDbi Q04089.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblFungii YDR440W ; YDR440W ; YDR440W .
    GeneIDi 852050.
    KEGGi sce:YDR440W.

    Organism-specific databases

    CYGDi YDR440w.
    SGDi S000002848. DOT1.

    Phylogenomic databases

    eggNOGi NOG294902.
    GeneTreei ENSGT00390000013515.
    HOGENOMi HOG000112251.
    KOi K11427.
    OMAi YTRSIHP.
    OrthoDBi EOG7KH9VN.

    Enzyme and pathway databases

    BioCyci YEAST:G3O-29974-MONOMER.

    Miscellaneous databases

    EvolutionaryTracei Q04089.
    NextBioi 970311.
    PROi Q04089.

    Gene expression databases

    Genevestigatori Q04089.

    Family and domain databases

    Gene3Di 3.40.50.150. 1 hit.
    InterProi IPR013110. DOT1.
    IPR025789. Histone_H3-K79_MeTrfase.
    IPR021162. Histone_H3-K79_MeTrfase_fungi.
    IPR029063. SAM-dependent_MTases-like.
    [Graphical view ]
    Pfami PF08123. DOT1. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF017570. Histone_H3-K79_MeTrfase. 1 hit.
    SUPFAMi SSF53335. SSF53335. 1 hit.
    PROSITEi PS51569. DOT1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. Cited for: FUNCTION.
    10. 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.

    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: October 1, 2014
    This is version 132 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

    External Data

    Dasty 3