DOT1_COCIM
ID DOT1_COCIM Reviewed; 499 AA.
AC Q1DKD8; J3K2K7;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 97.
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; ORFNames=CIMG_09225;
OS Coccidioides immitis (strain RS) (Valley fever fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Onygenales; Onygenaceae; Coccidioides.
OX NCBI_TaxID=246410;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=RS;
RX PubMed=19717792; DOI=10.1101/gr.087551.108;
RA Sharpton T.J., Stajich J.E., Rounsley S.D., Gardner M.J., Wortman J.R.,
RA Jordar V.S., Maiti R., Kodira C.D., Neafsey D.E., Zeng Q., Hung C.-Y.,
RA McMahan C., Muszewska A., Grynberg M., Mandel M.A., Kellner E.M.,
RA Barker B.M., Galgiani J.N., Orbach M.J., Kirkland T.N., Cole G.T.,
RA Henn M.R., Birren B.W., Taylor J.W.;
RT "Comparative genomic analyses of the human fungal pathogens Coccidioides
RT and their relatives.";
RL Genome Res. 19:1722-1731(2009).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=RS;
RX PubMed=20516208; DOI=10.1101/gr.103911.109;
RA Neafsey D.E., Barker B.M., Sharpton T.J., Stajich J.E., Park D.J.,
RA Whiston E., Hung C.-Y., McMahan C., White J., Sykes S., Heiman D.,
RA Young S., Zeng Q., Abouelleil A., Aftuck L., Bessette D., Brown A.,
RA FitzGerald M., Lui A., Macdonald J.P., Priest M., Orbach M.J.,
RA Galgiani J.N., Kirkland T.N., Cole G.T., Birren B.W., Henn M.R.,
RA Taylor J.W., Rounsley S.D.;
RT "Population genomic sequencing of Coccidioides fungi reveals recent
RT hybridization and transposon control.";
RL Genome Res. 20:938-946(2010).
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; GG704915; EAS28021.3; -; Genomic_DNA.
DR RefSeq; XP_001239604.1; XM_001239603.2.
DR AlphaFoldDB; Q1DKD8; -.
DR SMR; Q1DKD8; -.
DR STRING; 246410.Q1DKD8; -.
DR EnsemblFungi; EAS28021; EAS28021; CIMG_09225.
DR GeneID; 4558580; -.
DR KEGG; cim:CIMG_09225; -.
DR VEuPathDB; FungiDB:CIMG_09225; -.
DR InParanoid; Q1DKD8; -.
DR OMA; WSDSVSW; -.
DR OrthoDB; 649516at2759; -.
DR Proteomes; UP000001261; Unassembled WGS sequence.
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; Reference proteome;
KW Repeat; S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW Transferase.
FT CHAIN 1..499
FT /note="Histone-lysine N-methyltransferase, H3 lysine-79
FT specific"
FT /id="PRO_0000270609"
FT DOMAIN 178..499
FT /note="DOT1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT REGION 1..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 31..46
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 305..308
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 328..337
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 354
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 390..391
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
SQ SEQUENCE 499 AA; 55825 MW; A436A6A833DC4099 CRC64;
MSFFDHLQKK GVGAIQAQKV QIRKVERKPS KVVSSSSSSS IAKPQRRLDT VSKPVAARRS
ASSASKPARH PQPRSRPPSR KRNTIEPTLF GSSEESDTDV SLDLRITKRA RVSSSVEPDL
HRRVRDTDAF SDGEAAFDMI HAADIISSKK SLGFNNAFGI EDGPIIVELQ YPGAPQKERY
QLVVPRDNDG FKPLDDIVQV LEIVSQNYIS EEHLALFEDE SNGLLRRLRR ALSNTSLTDF
LDGVKSYNET IQRLHQDGSI SRHLDSKHAL ALPLVERILT QVYSRTVSPR VDSLRQYENG
SDNVYGELLP RLVSKIFAET RLKSDQVFVD LGSGVGNVVL QAALEIGCES WGCEMMQNAC
DLAELQEKEF KTRCRLWGLQ PGQTHLKRGD FLEVDSVGKI LQKADVVLIN NQAFTPELNH
KLVNYFLDMK EGCQIVSLKS FVPAGHRIQS RNLNSPINLL SVKQKQYWSD SVSWTNAAGT
YFIATKDSSR LKAFLESST
