ID A0A2K5N2G1_CERAT Unreviewed; 1507 AA.
AC A0A2K5N2G1;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 28-MAR-2018, sequence version 1.
DT 24-JAN-2024, entry version 31.
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:ENSCATP00000031659.1};
OS Cercocebus atys (Sooty mangabey) (Cercocebus torquatus atys).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Cercocebus.
OX NCBI_TaxID=9531 {ECO:0000313|Ensembl:ENSCATP00000031659.1, ECO:0000313|Proteomes:UP000233060};
RN [1] {ECO:0000313|Ensembl:ENSCATP00000031659.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-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 Ensembl; ENSCATT00000055925.1; ENSCATP00000031659.1; ENSCATG00000038916.1.
DR GeneTree; ENSGT00390000013515; -.
DR Proteomes; UP000233060; Unplaced.
DR Bgee; ENSCATG00000038916; Expressed in skeletal muscle tissue and 11 other cell types or tissues.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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:0031507; P:heterochromatin formation; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
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 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 Reference proteome {ECO:0000313|Proteomes:UP000233060};
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..298
FT /note="DOT1"
FT /evidence="ECO:0000259|PROSITE:PS51569"
FT REGION 303..397
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 753..820
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 860..879
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 924..1006
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1018..1074
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1112..1210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1250..1279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1301..1367
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 496..603
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 357..382
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 383..397
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 929..958
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 965..979
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1021..1035
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 104..107
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
FT BINDING 127..136
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
FT BINDING 154
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
FT BINDING 190..191
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
SQ SEQUENCE 1507 AA; 161571 MW; F7006CE2D2EAD59E CRC64;
WLVAVQPETT PWSLPCPCAL PSHACGSRPS LAFFSFESMQ RLCDKYNRAI DSIHQLWKGT
TQPMKLNTRP STGLLRHILQ QVYNHSVTDP EKLNNYEPFS PEVYGETSFD LVAQMIDEIK
MTDDDLFVDL GSGVGQVVLQ VAAATNCKHH YGVEKADIPA KYAETMDREF RKWMKWYGKK
HAEYTLERGD FLSEEWRERI ANTSVIFVNN FAFGPEVDHQ LKERFANMKE GGRIVSSKPF
APLNFRINSR NLSDIGTIMR VVELSPLKGS VSWTGKPVSY YLHTIDRTIR WGSPWLNPLS
FQEEQEAARR RQQRESKSNA ATPTKGPEGK LAGPTDAPMD SGAEEEKAGA ATVKKPSPSK
ARKKKLNKKG RKMAGRKRGR PKKMSTANPE RKPKKNQTAL DVLHAQTVSQ TAASSPQDAY
RSPHSPFYQL PPSVQRHSPN PLLVAPTPPA LQKLLESFKI QYLQFLAYTK TPQYKASLQE
LLGQEKEKNT QLLGAAQQLL SHCQAQKEEI RRLFQQKLDE LGVKALTYND LIQAQKEISA
HNQQLREQSE QLEQDNRALR SQSLQLLKAR CEELQLDWAT LSLEKLLKEK QALKSQISEK
QRHCLELQIS IVELEKSQRQ QELLQLKSCV PPDDALSLHL RGKGALGREL EPDASRLHLE
LDCAKFSLPH LSSMSPELSM NGQAAGYELC SALSRPSSKQ NTPQYLASPL DQEVVPCTPS
HGGRPRLEKL SGLAAPDYTR LSPAKIVLRR HLSQDHTVPG RPAASELHPR AEHTKENGLP
YQSPSVPGSM KLSPQDPRPL SPGALQLAGE KSSEKGLRER AYGSSGELIT SLPISIPLST
VQPNKLPVSI PLASVVLPSR AERARSTPSP VLQPRDPSST LEKQIGANAH GAASRSLALA
PAGFSYAGSV AISGALAGSP ASLTPGAEPA TLDESSSSGS LFATVGSRSS TPQHPLLLAQ
PRNSLPASPA HQLSSSPRLG GPAQGPLPEA SKGDLPSDSG FSDPESEAKR RIVFTIAAGA
GSARQSPSSK HSPLTASARG DCVPSHGQDS RKRGRRKRAS TGTPSLSAGV SPKRRALPSV
AGLFTQPSGS PLNLNSMVSN INQPLEITAI SSPETSLKSS PVPYQDHDQP PVLKKERPLS
QTNGAHYSPL TSDEEPGSED EPSSARIERK IATISLESKS PPKTLENGGG LAGRKPTPAS
EPVNNSKWKS TFSPISDIGL AKSADSPLQA SSALSQNSLF TFRPALEEPP ADAKLATHPR
KGFPGSLSGA DGLSPSTNPA NGCTFGGGLA ADLSLHSFSD GASLPHKGPE AAGLSSPLSF
PSQRGKEASD ANPFLSKRQL DGLAGLKGEG SRSKEAGEGG LQLCGPMDKT PLLTGKATKA
RDRELDLKNG HNLFISAAAV PPGSLLSGPG LAPVASSAGG AASSTQTHRP FLGPFPPGPQ
FALGPMSLQA NLGSVAGSSV LQSLFSSVPA AAGLVHVSSA ATRLTNSHAM GSFSGVAGST
VGGRQGR
//
