ID M3Y6F6_MUSPF Unreviewed; 1643 AA.
AC M3Y6F6;
DT 01-MAY-2013, integrated into UniProtKB/TrEMBL.
DT 01-MAY-2013, sequence version 1.
DT 27-MAR-2024, entry version 67.
DE RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-79 specific {ECO:0000256|ARBA:ARBA00020987, ECO:0000256|PIRNR:PIRNR037123};
GN Name=DOT1L {ECO:0000313|Ensembl:ENSMPUP00000006907.1};
OS Mustela putorius furo (European domestic ferret) (Mustela furo).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Musteloidea; Mustelidae;
OC Mustelinae; Mustela.
OX NCBI_TaxID=9669 {ECO:0000313|Ensembl:ENSMPUP00000006907.1};
RN [1] {ECO:0000313|Ensembl:ENSMPUP00000006907.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (MAR-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 -!- FUNCTION: Histone methyltransferase. Methylates 'Lys-79' of histone H3.
CC {ECO:0000256|PIRNR:PIRNR037123}.
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|PIRNR:PIRNR037123, 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|PIRNR:PIRNR037123,
CC ECO:0000256|RuleBase:RU271113}.
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DR EMBL; AEYP01093226; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR STRING; 9669.ENSMPUP00000006907; -.
DR Ensembl; ENSMPUT00000007021.1; ENSMPUP00000006907.1; ENSMPUG00000006962.1.
DR eggNOG; KOG3924; Eukaryota.
DR GeneTree; ENSGT00390000013515; -.
DR HOGENOM; CLU_004082_1_0_1; -.
DR InParanoid; M3Y6F6; -.
DR OMA; SEKQRRC; -.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0140956; F:histone H3K79 trimethyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IEA:UniProtKB-UniRule.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-UniRule.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0031507; P:heterochromatin formation; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; IEA:Ensembl.
DR CDD; cd02440; AdoMet_MTases; 1.
DR CDD; cd20902; CC_DOT1L; 1.
DR Gene3D; 1.10.260.60; -; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR InterPro; IPR025789; DOT1_dom.
DR InterPro; IPR021169; DOT1L/grappa.
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 PIRSF; PIRSF037123; Histone_H3-K79_MeTrfase_met; 1.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR PROSITE; PS51569; DOT1; 1.
PE 3: Inferred from homology;
KW Acetylation {ECO:0000256|ARBA:ARBA00022990};
KW Chromatin regulator {ECO:0000256|ARBA:ARBA00022853,
KW ECO:0000256|PIRNR:PIRNR037123}; Coiled coil {ECO:0000256|SAM:Coils};
KW Methyltransferase {ECO:0000256|ARBA:ARBA00022603,
KW ECO:0000256|PIRNR:PIRNR037123};
KW Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|PIRNR:PIRNR037123};
KW S-adenosyl-L-methionine {ECO:0000256|ARBA:ARBA00022691,
KW ECO:0000256|PIRNR:PIRNR037123};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR037123}.
FT DOMAIN 1..276
FT /note="DOT1"
FT /evidence="ECO:0000259|PROSITE:PS51569"
FT REGION 280..424
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 769..796
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 839..874
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 930..1052
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1088..1187
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1284..1363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1512..1532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 510..582
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 280..295
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..361
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 362..377
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 389..410
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 844..864
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 931..945
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1088..1102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1348..1363
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 82..85
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
FT BINDING 105..114
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
FT BINDING 132
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
FT BINDING 168..169
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
SQ SEQUENCE 1643 AA; 173883 MW; 59912F341FA587DC CRC64;
MENYVLIDYD TKSFESMQRL CDKYNRAIDS IHQLWKGTTQ PMKLNTRPSN GLLRHILQQV
YNHSVTDPEK LNNYEPFSPE VYGETSFDLV AQMIDEIKMT EDDLFVDLGS GVGQVVLQVA
AATNCKHHYG VEKADIPAKY AETMDREFRK WMKWYGKKHA EYTLERGDFL SEEWRERIAN
TSVIFVNNFA FGPEVDHQLK ERFANMKEGG RIVSSKPFAP LNFRINSRNL SDIGTIMRVV
ELSPLKGSVS WTGKPVSYYL HTIDRTILEN YFSSLKNPKL REEQEAARRR QQRESKSATT
TPTKGPESKA AASADAPTDS GAEEEKAGAT TIKKPSPSKA RKKKLNKKGR KMAGRKRGRP
KKMSTANPER KPKKSQTALD LLHAQAAPQT AAPSPQDAYK SPQSPFYQLP PSVQRHPPDQ
LLLAPTPPAL QKLLESFKIQ YLQFLAYTKT AQYKASLQQL LDQEKEKNAR LLGAAQQLFG
HCQAQKEEIK RLFQQKLDEL GVKALTYNDL IQAQKEISAH NQQLREQTEQ LQKDNGELRT
QSLRLLKARC EELKLDWSTL SLENLLKEKQ ALRTQISEKQ RHCLELQISI VELEKSQRRQ
ELLQLKSCVP PDDGLSAHLR GKGALGRELE AEPGRLHLDL DGPKFSLPHL SSASPELSMN
GHVAGYEVCG ALSRPSSKQN TPQYLASPLD QDVVPCTPSH GGRPRLEKMA GLALPDYTRL
SPAKLVLRRH LSQDHAAGGK PAAGELHPRA EHAKENGLPY QSPGIVNGIK LSPQDPRPSS
PAALQMTGER GSEKGVKERA YASSGEAITS LPVSIPLSTV QPSKLPVSIP LASVVLPSRA
EKVRSTPSPV SQTRESSSTL EKQMGANAHG AGSKNLAPAS TGFYTGSGAV SGALAGSPAP
LAPGAEPGTL DEVSSSGSLF AGMGSCGSAP QLPPLLQQSR SSGAASPAHP LCASPRLSSA
AQGPLPEANK GDLPSEAGVS DPEGEVKRRI VFTISAGGGA KQSPPGKPSP LPTGARGDSG
QGHGPDSRKR GRRKRAAAGT PSLSSGVSPK RRALPSVAGL FTQSSGSPLN LNSMVSNINQ
PLEITAISSP ESLKSSPVPY QDNDQPPVLK KEKPLSQTNG AHYSPLTSDE EQGSEDEPGS
ARIERKIATI SLESKSPPKT LESGGGLTGR KPAPASEPAN SSKWKSTFSP ISDLGLAKCA
DSPLQASSAL SQNSLFAFRP PLEEPGLADA KLAAHPRKGF PGALAGAGGL SPSSNPPNGF
AFSGGLTADL SLHSFSDGAS LSHKVPETAS LSGPLSFPTP RGKEGAAAEP GTFVNKRQLD
GLSGPKAREA GEPGLPACGP PDKASLTHSK PGKGRDREPD LKNGHNLFIS AATVPPGGLL
SGPGLATVAS STVSAAPSAQ THRPFLGTFA PGPQFALGPM SLQANLGSSV LQSLFSSVPA
AAGLVHVSSA ATRLTNSHAM GSFSSGVAGG AVGGVFNHAV PSASAHPFGA SFGSGAACRS
GTLGLTALQA VAPPPPPQGQ PALPAPPPPN AALPPAPALL PANSEPVLLQ NLASLPANQA
FLPASSAASL QPANASLSIK LTSLPHKAPR PSFTVHHQPL PGLALAQAAP VIPQAGSTGP
SAVWVSLGMP PPYAARLAGV KPR
//
