DOT1_NEUCR
ID DOT1_NEUCR Reviewed; 531 AA.
AC Q7SB74;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2003, sequence version 1.
DT 03-AUG-2022, 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=dot-1; ORFNames=NCU06266;
OS Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS FGSC 987).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX NCBI_TaxID=367110;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX PubMed=12712197; DOI=10.1038/nature01554;
RA Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT "The genome sequence of the filamentous fungus Neurospora crassa.";
RL Nature 422:859-868(2003).
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; CM002238; EAA33634.1; -; Genomic_DNA.
DR RefSeq; XP_962870.1; XM_957777.2.
DR AlphaFoldDB; Q7SB74; -.
DR SMR; Q7SB74; -.
DR STRING; 5141.EFNCRP00000005971; -.
DR EnsemblFungi; EAA33634; EAA33634; NCU06266.
DR GeneID; 3879023; -.
DR KEGG; ncr:NCU06266; -.
DR VEuPathDB; FungiDB:NCU06266; -.
DR HOGENOM; CLU_027287_2_0_1; -.
DR InParanoid; Q7SB74; -.
DR OMA; WSDSVSW; -.
DR Proteomes; UP000001805; Chromosome 3, Linkage Group III.
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 methyltransferase activity (H3-K79 specific); IBA:GO_Central.
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:0034729; P:histone H3-K79 methylation; IEA:InterPro.
DR GO; GO:2000677; P:regulation of transcription regulatory region DNA binding; IBA:GO_Central.
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; Reference proteome;
KW Repeat; S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW Transferase.
FT CHAIN 1..531
FT /note="Histone-lysine N-methyltransferase, H3 lysine-79
FT specific"
FT /id="PRO_0000270615"
FT DOMAIN 214..531
FT /note="DOT1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT REGION 1..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 10..27
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..106
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 352..355
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 375..384
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 401
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 437..438
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
SQ SEQUENCE 531 AA; 59294 MW; D1ED4AFD7EBDD1BB CRC64;
MSIFNQKSKF KIKTEIRTVR ETVERPKLKA STSSSSIPTT GSSQHSNVRI AGAGSSLSRA
SSTPRLNGTS HTTSTSSSAR ASLTKVTTIP TARRIQSASP IPSINGDGRS SRKRRAIKAS
SRSPISPHFS EDSDSDSNGD ENWEDNLDAR KRRKRVHDER PVDVNRKLRH PKIWKGEEAD
QVERIPGPAI IHAAKVASLE HKCKPALGLK NEEVAVRLQY PGARYPERYE LVEGKDKIDA
VKDIEKVVQL AASTYLTDEE GKIFLDHQTG ILRKLVKSKN RSDGPGFKAA LREYNDEFLK
LMRKGVIVRN LDKMHGIPRE LVDFILDQVY DRTVAPRVEL LAKYQNGSDN VYGELNHPFI
SDILERTNLT SDKVFVDLGS GVGNVTLQAA LEIGCESWGC EMMENACNLA EAQYDEFLAR
CRLWGVKPGK VRLERGDFRK NEKILEVLKR ADVVLVNNQA FTSQLNDNLV SMFLDLKIGC
KIISLKTFVH DNKNAENDVA TSILDVEHLT YPEGYVSWTG ASGTYCISTR R
