ID H9LAN6_MOUSE Unreviewed; 1736 AA.
AC H9LAN6;
DT 13-JUN-2012, integrated into UniProtKB/TrEMBL.
DT 13-JUN-2012, sequence version 1.
DT 08-NOV-2023, entry version 66.
DE RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-79 specific {ECO:0000256|ARBA:ARBA00020987, ECO:0000256|PIRNR:PIRNR037123};
GN Name=Dot1l {ECO:0000313|EMBL:ADZ40239.1, 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|EMBL:ADZ40239.1};
RN [1] {ECO:0000313|EMBL:ADZ40239.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=C57BL/6 {ECO:0000313|EMBL:ADZ40239.1};
RC TISSUE=Testis {ECO:0000313|EMBL:ADZ40239.1};
RA Kusumoto K., Okada Y.;
RT "Identification of a male haploid-specific transcript of DOT1L.";
RL Submitted (FEB-2011) to the EMBL/GenBank/DDBJ databases.
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; JF508521; ADZ40239.1; -; mRNA.
DR PeptideAtlas; H9LAN6; -.
DR UCSC; uc033frf.1; mouse.
DR AGR; MGI:2143886; -.
DR MGI; MGI:2143886; Dot1l.
DR ChiTaRS; Dot1l; mouse.
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: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; 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; 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 2: Evidence at transcript level;
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 16..330
FT /note="DOT1"
FT /evidence="ECO:0000259|PROSITE:PS51569"
FT REGION 334..465
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 784..857
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 891..930
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 964..1110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1143..1242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1284..1319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1349..1418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1586..1631
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 562..634
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 334..349
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 389..414
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 415..430
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 811..826
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 901..916
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 967..1026
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1052..1078
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1143..1160
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1349..1370
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1591..1631
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 136..139
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
FT BINDING 159..168
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
FT BINDING 186
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
FT BINDING 222..223
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
SQ SEQUENCE 1736 AA; 185300 MW; 02C56157B3D72A68 CRC64;
MGEKLELRLK SPVGAESAVY PWPLPVYDKH HDAAHEIIET IRWVCEEIPD LKLAMENYVL
IDYDTKSFES MQRLCDKYNR AIDSIHQLWK GTTQPMKLNT RPSNGLLRHI LQQVYNHSVT
DPEKLNNYEP FSPEVYGETS FDLVAQMIDE IKMTEDDLFV DLGSGVGQVV LQVAAATNCK
HHYGVEKADI PAKYAETMDR EFRKWMKWYG KKHAEYTLER GDFLSEEWRE RIANTSVIFV
NNFAFGPEVD HQLKERFANM KEGGRIVSSK PFAPLNFRIN SRNLSDIGTI MRVVELSPLK
GSVSWTGKPV SYYLHTIDRT ILENYFSSLK NPKLREEQEA ARRRQQRENK SNATTPTKVP
ESKAAATEAP ADSGAEEEKS GVATVKKPSP SKARKKKLNK KGRKMAGRKR GRPKKMSAAS
AERKSKKSQS TLDLLHSPPP APPSASPQDA YRAPHSPFYQ LPPSTQLHSP NPLLVAPTPP
ALQKLLESFR IQYLQFLAYT KTPQYKANLQ QLLDQEKEKN TQLLGTAQQL FGHCQAQKEE
IRRLFQQKLD ELGVKALTYN DLIQAQKEIS AHNQQLREQS EQLEKDNSEL RSQSLRLLRA
RCEELRLDWS TLSLENLRKE KQALRSQISE KQRHCLELQI SIVELEKTQR QQELLQLKSC
VPPDDALSLH LRGKGALGRE LEADAGRLRL ELDCAKISLP HLSSMSPELS MNGHAASYEL
CNAASRPSSK QNTPQYLASP LDQEVVPCTP SHSGRPRLEK LSGLALPDYT RLSPAKIVLR
RHLSQDHTGA SKAATSEPHP RPEHPKESSL PYQSPGLSNS MKLSPQDPPL ASPATSPLTS
EKGSEKGVKE RAYSSHGETI TSLPVSIPLS TVQPNKLPVS IPLASVVLPS RAERARSTPS
PVPQPRDSSA TLEKQTGASA HGAGGAGAGS RSLAVAPTGF YAGSVAISGA LASSPAPLAS
GMESAVFDES SGPSSLFATM GSRSTPPQHP PLLSQSRNSG PASPAHQLTA SPRLSVTTQG
SLPDTSKGEL PSDPAFSDPE SEAKRRIVFS ISVGASSKQS PSTRHSPLTS GTRGDCVQSH
GQDSRKRSRR KRASAGTPSL STGVSPKRRA LPTVAGLFTQ SSGSPLNLNS MVSNINQPLE
ITAISSPESS LKSSPTPYQD HDQPPVLRKE RPLGLTNGAH YSPLTSDEEP GSEDEPSSAR
IERKIATISL ESKSPPKTLE NGGGLVGRKS APSSEPINSS KWKSTFSPIS DLGLAKAVDS
PLQAGSALSH SPLFSFRPSL EEPAAEAKLP THPRKSFAGS LGAAEGPSPG TNPPNGLAFS
GGLAADLGLH SFNDGASLSH KGPDVTGLSA SLSFPSQRGK DSTTEANPFL SRRQPEGLGG
LKGEGNANKE SGESLPLCGP SDKASLPHGS RASKGRDREL DFKGGHNLFI SAAAVPPGGL
LGGPGLVTVA SSAGSATPTA QAPRPFLSTF APGPQFTLGP MSLQANLGSV AGSSVLQSLF
STVPAAAGLV HVSSTATRLT NSHTMGSFSS GVAGGTVGGV FTHAVPSASA HPFGAGVGSG
AVCSSATLGL SPLQAAASTS ASSFQAAASV ETRPPPPPPL LPPQHLGRPP AGPPVLHAPP
PPNVALPPPP ALLASNPEPV LLQSLASLPA NNAFLPPSSA ASLQPANASL SVKLASLPHK
VSRPSFTVHH QPLPRLALAQ AAPAAPQAST SGPSAVWVSL GMPPPYAAHL SGVKPR
//
