ID   DOT1_CRYNB              Reviewed;         644 AA.
AC   P0CN15; Q55K55; Q5K9E4;
DT   28-JUN-2011, integrated into UniProtKB/Swiss-Prot.
DT   28-JUN-2011, sequence version 1.
DT   03-AUG-2022, entry version 51.
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=CNBK1310;
OS   Cryptococcus neoformans var. neoformans serotype D (strain B-3501A)
OS   (Filobasidiella neoformans).
OC   Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes;
OC   Tremellales; Cryptococcaceae; Cryptococcus;
OC   Cryptococcus neoformans species complex.
OX   NCBI_TaxID=283643;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=B-3501A;
RX   PubMed=15653466; DOI=10.1126/science.1103773;
RA   Loftus B.J., Fung E., Roncaglia P., Rowley D., Amedeo P., Bruno D.,
RA   Vamathevan J., Miranda M., Anderson I.J., Fraser J.A., Allen J.E.,
RA   Bosdet I.E., Brent M.R., Chiu R., Doering T.L., Donlin M.J., D'Souza C.A.,
RA   Fox D.S., Grinberg V., Fu J., Fukushima M., Haas B.J., Huang J.C.,
RA   Janbon G., Jones S.J.M., Koo H.L., Krzywinski M.I., Kwon-Chung K.J.,
RA   Lengeler K.B., Maiti R., Marra M.A., Marra R.E., Mathewson C.A.,
RA   Mitchell T.G., Pertea M., Riggs F.R., Salzberg S.L., Schein J.E.,
RA   Shvartsbeyn A., Shin H., Shumway M., Specht C.A., Suh B.B., Tenney A.,
RA   Utterback T.R., Wickes B.L., Wortman J.R., Wye N.H., Kronstad J.W.,
RA   Lodge J.K., Heitman J., Davis R.W., Fraser C.M., Hyman R.W.;
RT   "The genome of the basidiomycetous yeast and human pathogen Cryptococcus
RT   neoformans.";
RL   Science 307:1321-1324(2005).
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; AAEY01000052; EAL18110.1; -; Genomic_DNA.
DR   RefSeq; XP_772757.1; XM_767664.1.
DR   AlphaFoldDB; P0CN15; -.
DR   SMR; P0CN15; -.
DR   EnsemblFungi; EAL18110; EAL18110; CNBK1310.
DR   GeneID; 4938827; -.
DR   KEGG; cnb:CNBK1310; -.
DR   VEuPathDB; FungiDB:CNBK1310; -.
DR   HOGENOM; CLU_027287_1_0_1; -.
DR   Proteomes; UP000001435; Chromosome 11.
DR   GO; GO:0000781; C:chromosome, telomeric region; IEA:GOC.
DR   GO; GO:0000786; C:nucleosome; IEA:InterPro.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0042393; F:histone binding; IEA:InterPro.
DR   GO; GO:0031151; F:histone methyltransferase activity (H3-K79 specific); IEA:InterPro.
DR   GO; GO:0000077; P:DNA damage checkpoint signaling; IEA:InterPro.
DR   GO; GO:0006281; P:DNA repair; IEA:InterPro.
DR   GO; GO:0034729; P:histone H3-K79 methylation; IEA:InterPro.
DR   GO; GO:0031509; P:subtelomeric heterochromatin assembly; IEA:InterPro.
DR   Gene3D; 3.40.50.150; -; 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; PTHR21451; 1.
DR   Pfam; PF08123; DOT1; 1.
DR   PIRSF; PIRSF017570; Histone_H3-K79_MeTrfase; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
DR   PROSITE; PS51569; DOT1; 1.
PE   3: Inferred from homology;
KW   Chromatin regulator; Methyltransferase; Nucleus; Repeat;
KW   S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW   Transferase.
FT   CHAIN           1..644
FT                   /note="Histone-lysine N-methyltransferase, H3 lysine-79
FT                   specific"
FT                   /id="PRO_0000410061"
FT   DOMAIN          297..637
FT                   /note="DOT1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT   REGION          21..152
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        21..79
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        93..107
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        129..144
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         442..445
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT   BINDING         465..474
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT   BINDING         491
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT   BINDING         528..529
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
SQ   SEQUENCE   644 AA;  71284 MW;  DEDBFAA9203F09C8 CRC64;
     MFSFFGDESK LPASTVMVSR MTVKKQAAAR QQSSGPMAGP SKPSNVTPKH SHGSLKGTPR
     SASEKGTPKQ GPSSSSKSTS KVKQEERIRP STIPRTPASS SSPGRLKRKT PKVQVVESES
     SSGSESSDDA LDSKPKRPKV TRKETGIDMT PLPGEQVVGR RVFCWDKVDM RGEWGRGWAG
     FVGCDEVVRG NVQGWANGGG GDGSKNLGKY RAFFPQEGFD RDGDFLPSVE VLYPAKGCRE
     KFVLMVPSSD REFNPIGELR NTLRLILEHY IPPSHRHIFG NLAESLDISN PLSSLPSRMT
     TPLPNSLVTP PPDPASPSPA FAFEISATST PAPSTERQET IADLIRKSLA PNRRDGPLFV
     TAIERYNSAM QAIQEDGTLQ QWLDEGMNGG KGIKVREWAA LVDFVHDQAY SRVVGGYSHE
     LEHHPKHPEE VSKAISGKED AYGELRHAFM SKIIEQTKLG PDSVFVDLGS GVGNCVLQAS
     LQAGSRSYGF ELLPVPAHCA RLQVREVQRR WAMWALKGNL DVEVHEGDFR VHKEVGRRLR
     EADVVLVNNE VFPSSLNMDL ADMFLDLKEG AKIVSLKPFV PEGFRMNESN CDSFAAILRS
     TQHDYYRDWV SWKGEWGNYY VAVIDRSRRI KFEESMTGRA SRRR