ID F7CVL0_MOUSE Unreviewed; 1202 AA.
AC F7CVL0;
DT 27-JUL-2011, integrated into UniProtKB/TrEMBL.
DT 27-JUL-2011, sequence version 1.
DT 27-MAR-2024, entry version 86.
DE RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-79 specific {ECO:0000256|ARBA:ARBA00020987, ECO:0000256|RuleBase:RU271113};
DE EC=2.1.1.360 {ECO:0000256|ARBA:ARBA00012190, ECO:0000256|RuleBase:RU271113};
DE AltName: Full=Histone H3-K79 methyltransferase {ECO:0000256|ARBA:ARBA00029821, ECO:0000256|RuleBase:RU271113};
DE Flags: Fragment;
GN Name=Dot1l {ECO:0000313|Ensembl:ENSMUSP00000116581.2,
GN ECO:0000313|MGI:MGI:2143886};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000313|Ensembl:ENSMUSP00000116581.2, ECO:0000313|Proteomes:UP000000589};
RN [1] {ECO:0000313|Ensembl:ENSMUSP00000116581.2, ECO:0000313|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000313|Ensembl:ENSMUSP00000116581.2,
RC ECO:0000313|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2] {ECO:0007829|PubMed:21183079}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [3] {ECO:0000313|Ensembl:ENSMUSP00000116581.2}
RP IDENTIFICATION.
RC STRAIN=C57BL/6J {ECO:0000313|Ensembl:ENSMUSP00000116581.2};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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:0000256|RuleBase:RU271113}.
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:0000256|ARBA:ARBA00001569,
CC ECO:0000256|RuleBase:RU271113};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000256|ARBA:ARBA00004123,
CC ECO:0000256|RuleBase:RU271113}.
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 {ECO:0000256|RuleBase:RU271113}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. DOT1 family. {ECO:0000256|RuleBase:RU271113}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR AlphaFoldDB; F7CVL0; -.
DR SMR; F7CVL0; -.
DR jPOST; F7CVL0; -.
DR MaxQB; F7CVL0; -.
DR PeptideAtlas; F7CVL0; -.
DR ProteomicsDB; 316564; -.
DR Antibodypedia; 22937; 606 antibodies from 32 providers.
DR Ensembl; ENSMUST00000150338.8; ENSMUSP00000116581.2; ENSMUSG00000061589.15.
DR UCSC; uc007gen.1; mouse.
DR AGR; MGI:2143886; -.
DR MGI; MGI:2143886; Dot1l.
DR VEuPathDB; HostDB:ENSMUSG00000061589; -.
DR GeneTree; ENSGT00390000013515; -.
DR HOGENOM; CLU_004082_0_0_1; -.
DR ChiTaRS; Dot1l; mouse.
DR Proteomes; UP000000589; Chromosome 10.
DR Bgee; ENSMUSG00000061589; Expressed in cerebellar cortex and 226 other cell types or tissues.
DR ExpressionAtlas; F7CVL0; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
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:0042054; F:histone methyltransferase activity; IDA:MGI.
DR GO; GO:0003676; F:nucleic acid binding; ISO:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:MGI.
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:0010467; P:gene expression; IDA:MGI.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; ISO:MGI.
DR CDD; cd20902; CC_DOT1L; 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 1: Evidence at protein level;
KW Chromatin regulator {ECO:0000256|ARBA:ARBA00022853,
KW ECO:0000256|RuleBase:RU271113}; Coiled coil {ECO:0000256|SAM:Coils};
KW Methyltransferase {ECO:0000256|ARBA:ARBA00022603,
KW ECO:0000256|RuleBase:RU271113};
KW Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|RuleBase:RU271113};
KW Proteomics identification {ECO:0007829|EPD:F7CVL0,
KW ECO:0007829|MaxQB:F7CVL0};
KW Reference proteome {ECO:0000313|Proteomes:UP000000589};
KW S-adenosyl-L-methionine {ECO:0000256|ARBA:ARBA00022691,
KW ECO:0000256|RuleBase:RU271113};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|RuleBase:RU271113}.
FT DOMAIN 1..113
FT /note="DOT1"
FT /evidence="ECO:0000259|PROSITE:PS51569"
FT REGION 117..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 567..640
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 674..715
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 737..911
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 926..1000
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1052..1097
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 345..417
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 117..132
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 172..197
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 198..213
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 594..609
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 684..699
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 750..809
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 835..861
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 926..943
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1057..1097
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT NON_TER 1
FT /evidence="ECO:0000313|Ensembl:ENSMUSP00000116581.2"
SQ SEQUENCE 1202 AA; 128714 MW; 81713E01350D4364 CRC64;
LERGDFLSEE WRERIANTSV IFVNNFAFGP EVDHQLKERF ANMKEGGRIV SSKPFAPLNF
RINSRNLSDI GTIMRVVELS PLKGSVSWTG KPVSYYLHTI DRTILENYFS SLKNPKLREE
QEAARRRQQR ENKSNATTPT KVPESKAAAT EAPADSGAEE EKSGVATVKK PSPSKARKKK
LNKKGRKMAG RKRGRPKKMS AASAERKSKK SQSTLDLLHS PPPAPPSASP QDAYRAPHSP
FYQLPPSTQL HSPNPLLVAP TPPALQKLLE SFRIQYLQFL AYTKTPQYKA NLQQLLDQEK
EKNTQLLGTA QQLFGHCQAQ KEEIRRLFQQ KLDELGVKAL TYNDLIQAQK EISAHNQQLR
EQSEQLEKDN SELRSQSLRL LRARCEELRL DWSTLSLENL RKEKQALRSQ ISEKQRHCLE
LQISIVELEK TQRQQELLQL KSCVPPDDAL SLHLRGKGAL GRELEADAGR LRLELDCAKI
SLPHLSSMSP ELSMNGHAAS YELCNAASRP SSKQNTPQYL ASPLDQEVVP CTPSHSGRPR
LEKLSGLALP DYTRLSPAKI VLRRHLSQDH TGASKAATSE PHPRPEHPKE SSLPYQSPGL
SNSMKLSPQD PPLASPATSP LTSEKGSEKG VKERAYSSHG ETITSLPVSI PLSTVQPNKL
PVSIPLASVV LPSRAERARS TPSPVPQPRD SSATLEKQTG ASAHGAGGAG AGSRSLAVAP
TGFYAGSVAI SGALASSPAP LASGMESAVF DESSGPSSLF ATMGSRSTPP QHPPLLSQSR
NSGPASPAHQ LTASPRLSVT TQGSLPDTSK GELPSDPAFS DPESEAKRRI VFSISVGASS
KQSPSTRHSP LTSGTRGDCV QSHGQDSRKR SRRKRASAGT PSLSTGVSPK RRALPTVAGL
FTQSSGSPLN LNSMVSNINQ PLEITAISSP ESSLKSSPTP YQDHDQPPVL RKERPLGLTN
GAHYSPLTSD EEPGSEDEPS SARIERKIAT ISLESKSPPK TLENGVFTHA VPSASAHPFG
AGVGSGAVCS SATLGLSPLQ AAASTSASSF QAAASVETRP PPPPPLLPPQ HLGRPPAGPP
VLHAPPPPNV ALPPPPALLA SNPEPVLLQS LASLPANNAF LPPSSAASLQ PANASLSVKL
ASLPHKVSRP SFTVHHQPLP RLALAQAAPA APQASTSGPS AVWVSLGMPP PYAAHLSGVK
PR
//
