ID DOT1_CANAL Reviewed; 1343 AA.
AC Q5A309; A0A1D8PKG3;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 27-MAR-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=CAALFM_C306300WA; ORFNames=CaO19.7402;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
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; CP017625; AOW28637.1; -; Genomic_DNA.
DR RefSeq; XP_716067.1; XM_710974.1.
DR AlphaFoldDB; Q5A309; -.
DR SMR; Q5A309; -.
DR STRING; 237561.Q5A309; -.
DR EnsemblFungi; C3_06300W_A-T; C3_06300W_A-T-p1; C3_06300W_A.
DR GeneID; 3642236; -.
DR KEGG; cal:CAALFM_C306300WA; -.
DR CGD; CAL0000184097; DOT1.
DR VEuPathDB; FungiDB:C3_06300W_A; -.
DR eggNOG; KOG3924; Eukaryota.
DR HOGENOM; CLU_004528_0_0_1; -.
DR InParanoid; Q5A309; -.
DR OMA; NFIPPRY; -.
DR OrthoDB; 146338at2759; -.
DR Proteomes; UP000000559; Chromosome 3.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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 Gene3D; 1.10.260.170; -; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
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 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..1343
FT /note="Histone-lysine N-methyltransferase, H3 lysine-79
FT specific"
FT /id="PRO_0000270606"
FT DOMAIN 987..1304
FT /note="DOT1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 210..236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 418..439
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1110..1113
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 1133..1142
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 1160
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 1197..1198
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
SQ SEQUENCE 1343 AA; 155678 MW; D4DE4546A3DD562C CRC64;
MISGHLQTPD SSDHSGDEAK LTKPSGLESK TNELWSSDLE EELESRIMQP ATFSSILKQF
PSISEETIIS KIMSNKNCDK NNWKKKIYCY RYFLQPSKEE PDVGNMKSLV EKLEKLKLKK
WSASEIEQLF CNYLEDLTTS AVKVSIPGKT LDEVAAAVNN IHPRPRWTRK EIECLIKNEN
DFKKLEKDLF VRDLDSIKKK IRRDNLSIQN EIQDSEKKSP QSTDSNNKDS SRDLSRKERD
QLKKLLSKPI CFSELLAKFP GHSWEYIARE IIQLDSSEDN TIWLKKIYYY CVVYSISVDK
EITKYIGGGN RIYEKVRSDW SKIKTLDFFK DWSLQEFERL YCFAFHDLTK SALTKNFPSK
NLNDICKVVN ISFPKVPYTD REMKYLERHL DTPMQTLENN LPFRSRGSIH KKLEALKALT
ETTEQKQPPT KTRPKNEEEK NVENAAYMKE LIMFDLTLEA IENTFPSEPI EEIIKEIKNS
EIFDPLSFTR GEKELMAKLV KKGNLIDDCF DYFPLREEEF IRSKYAEAEY VSGRKMKFNT
PEERLAYEAK WTLFNMGKQE YGRGNRRSTK RYCEIDELSK LEQEASVKRS KKKIELTEEE
LEQRRKRSEH FRLCRLKKLE EKREKYRIEK AKRLEKIAAG LIKPSTSGYE LKDIVTSAEY
FQSIVGDKQK VQEGQKRKRI QTEYFAPEFI EKPKAVKLKT TKRQAEKNKI KKQLKREAQL
KIKKKKTIAP KKGKRRVKTN NGIIEEIKDV YKLSSEPYVE SEVEEEDEEE DYISPYDPPD
IISDSQVKLN GRHLYISSFY KELPEIPELK FVSLPHMEMS GNDITVAKQI MTTANDDILY
DDCLAYEIVA QHIKSYRDLP ISFPPVLDPI THELNSANIV RIRFFLYPEH YESFMLASPK
SNELDPVHEI AKLFMIQYSL YFSHSDTLKK IITEDYCHKL EHSVEENDFG EFMFVVDKWN
QLVMKLSPNL ASVQNILGLK EDINEAPRAY LNQQEVSIPT NSDLKIETFY DEIMYESASP
LFNPINSNLE IDSESAPIPL GEVEIPNNVI EEINEKMPDN YIPDFFRRLK EKTEVSRYAM
QQILLRVYSR VVSTDSRKLR SYKAFTAETY GELLPSFTSE VLEKLNLLPT QKFYDLGSGV
GNTTFQAALE FGACSSGGCE IMEHASKLTE LQAGLIQKHL AVLGLQKLNL DFALHESFVG
NEKVRASCLD CDVLIINNYL FDGQLNDEVG KLLYGLRPGT KIVSLRNFIS PRYRATFDTV
FDFLSVEKHE MSDIMSVSWT ANKVPYYIST VEETIPREYL SREETKETSG KSKSVSPVGE
IENVAAAMMT PPTDSSESEI IKN
//
