ID   DOT1_YARLI              Reviewed;         492 AA.
AC   Q6C4Y5;
DT   09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2004, sequence version 1.
DT   24-JAN-2024, entry version 108.
DE   RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-79 specific;
DE            EC=2.1.1.360;
DE   AltName: Full=Histone H3-K79 methyltransferase;
DE            Short=H3-K79-HMTase;
GN   Name=DOT1; OrderedLocusNames=YALI0E22715g;
OS   Yarrowia lipolytica (strain CLIB 122 / E 150) (Yeast) (Candida lipolytica).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Dipodascaceae; Yarrowia.
OX   NCBI_TaxID=284591;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=CLIB 122 / E 150;
RX   PubMed=15229592; DOI=10.1038/nature02579;
RA   Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I.,
RA   de Montigny J., Marck C., Neuveglise C., Talla E., Goffard N., Frangeul L.,
RA   Aigle M., Anthouard V., Babour A., Barbe V., Barnay S., Blanchin S.,
RA   Beckerich J.-M., Beyne E., Bleykasten C., Boisrame A., Boyer J.,
RA   Cattolico L., Confanioleri F., de Daruvar A., Despons L., Fabre E.,
RA   Fairhead C., Ferry-Dumazet H., Groppi A., Hantraye F., Hennequin C.,
RA   Jauniaux N., Joyet P., Kachouri R., Kerrest A., Koszul R., Lemaire M.,
RA   Lesur I., Ma L., Muller H., Nicaud J.-M., Nikolski M., Oztas S.,
RA   Ozier-Kalogeropoulos O., Pellenz S., Potier S., Richard G.-F.,
RA   Straub M.-L., Suleau A., Swennen D., Tekaia F., Wesolowski-Louvel M.,
RA   Westhof E., Wirth B., Zeniou-Meyer M., Zivanovic Y., Bolotin-Fukuhara M.,
RA   Thierry A., Bouchier C., Caudron B., Scarpelli C., Gaillardin C.,
RA   Weissenbach J., Wincker P., Souciet J.-L.;
RT   "Genome evolution in yeasts.";
RL   Nature 430:35-44(2004).
CC   -!- FUNCTION: Histone methyltransferase that specifically trimethylates
CC       histone H3 to form H3K79me3. This methylation is required for telomere
CC       silencing and for the pachytene checkpoint during the meiotic cell
CC       cycle by allowing the recruitment of RAD9 to double strand breaks.
CC       Nucleosomes are preferred as substrate compared to free histone.
CC       {ECO:0000250|UniProtKB:Q04089}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl(79)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+)
CC         + N(6),N(6),N(6)-trimethyl-L-lysyl(79)-[histone H3] + 3 S-adenosyl-L-
CC         homocysteine; Xref=Rhea:RHEA:60328, Rhea:RHEA-COMP:15549, Rhea:RHEA-
CC         COMP:15552, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.360;
CC         Evidence={ECO:0000250|UniProtKB:Q04089, ECO:0000255|PROSITE-
CC         ProRule:PRU00902};
CC   -!- ACTIVITY REGULATION: Ubiquitination of histone H2B to form H2BK123ub1
CC       is required for efficient DOT1 methyltransferase activity on histone
CC       H3. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC   -!- MISCELLANEOUS: In contrast to other lysine histone methyltransferases,
CC       it does not contain a SET domain, suggesting the existence of another
CC       mechanism for methylation of lysine residues of histones.
CC   -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC       superfamily. DOT1 family. {ECO:0000255|PROSITE-ProRule:PRU00902}.
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DR   EMBL; CR382131; CAG79874.1; -; Genomic_DNA.
DR   RefSeq; XP_504277.1; XM_504277.1.
DR   AlphaFoldDB; Q6C4Y5; -.
DR   SMR; Q6C4Y5; -.
DR   STRING; 284591.Q6C4Y5; -.
DR   EnsemblFungi; CAG79874; CAG79874; YALI0_E22715g.
DR   GeneID; 2912906; -.
DR   KEGG; yli:YALI0E22715g; -.
DR   VEuPathDB; FungiDB:YALI0_E22715g; -.
DR   HOGENOM; CLU_027287_2_0_1; -.
DR   InParanoid; Q6C4Y5; -.
DR   OMA; IMEMTAL; -.
DR   OrthoDB; 146338at2759; -.
DR   Proteomes; UP000001300; Chromosome E.
DR   GO; GO:0000781; C:chromosome, telomeric region; IEA:GOC.
DR   GO; GO:0000786; C:nucleosome; IEA:InterPro.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0042393; F:histone binding; IEA:InterPro.
DR   GO; GO:0031151; F:histone H3K79 methyltransferase activity; IBA:GO_Central.
DR   GO; GO:0140956; F:histone H3K79 trimethyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0000077; P:DNA damage checkpoint signaling; IBA:GO_Central.
DR   GO; GO:0006281; P:DNA repair; IBA:GO_Central.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0031509; P:subtelomeric heterochromatin formation; IEA:InterPro.
DR   CDD; cd02440; AdoMet_MTases; 1.
DR   Gene3D; 1.10.260.170; -; 1.
DR   Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR   InterPro; IPR021162; Dot1.
DR   InterPro; IPR025789; DOT1_dom.
DR   InterPro; IPR030445; H3-K79_meTrfase.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   PANTHER; PTHR21451; HISTONE H3 METHYLTRANSFERASE; 1.
DR   PANTHER; PTHR21451:SF0; HISTONE-LYSINE N-METHYLTRANSFERASE, H3 LYSINE-79 SPECIFIC; 1.
DR   Pfam; PF08123; DOT1; 1.
DR   PIRSF; PIRSF017570; Histone_H3-K79_MeTrfase; 1.
DR   SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR   PROSITE; PS51569; DOT1; 1.
PE   3: Inferred from homology;
KW   Chromatin regulator; Methyltransferase; Nucleus; Reference proteome;
KW   Repeat; S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW   Transferase.
FT   CHAIN           1..492
FT                   /note="Histone-lysine N-methyltransferase, H3 lysine-79
FT                   specific"
FT                   /id="PRO_0000270617"
FT   DOMAIN          168..491
FT                   /note="DOT1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT   REGION          1..101
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        70..85
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         297..300
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT   BINDING         320..329
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT   BINDING         346
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT   BINDING         382..383
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
SQ   SEQUENCE   492 AA;  53624 MW;  32609F4429A5D9F6 CRC64;
     MFFSHLGKKN GGPTAKSSDV KRKVTKVKTR KPVVTSVSKS PSPSKTAPPP ATAAAAATAA
     AKPSTPRKSR RKTPNIYQLS KSSLSEVDTE ESEREVSSSL STPGLYELVP RDIVTAGFGS
     AELATSIHIT NASESGNLSM TDIYEPVSTD KSLSDRVKLG ALSCDFVEDY SLIKPKVPGE
     FEPVREILSI MEMTALHFVD KGASEEIKHP VMDDCIMRRF RRSYEGGDLE GMKTSMKEFD
     EVVKTQRAEG AILANLKQLT AVPQDLAYFL LNQVYSRIVS PESKSLRDYK AFSNNVYGEL
     MPPFMSTVFQ KTDLQPSSVF VDLGSGVGNC TLQAALEVGC ESWGCEVMTN ASSLAEKQKI
     ELYSRAKMFG IKTGDIHLVA SSFVHNDEVH SAISRADVLL VNNYAFDGTL NAHLLDMFLD
     LKEGCKIVSL KSFVPVGHVI SEHNIESPVN ILKVQKLDFY SGSVSWTAAG GTYYISTVDR
     SAIKAFLSKG GY
//