ID I3MHN1_ICTTR Unreviewed; 1732 AA.
AC I3MHN1;
DT 11-JUL-2012, integrated into UniProtKB/TrEMBL.
DT 22-NOV-2017, sequence version 2.
DT 27-MAR-2024, entry version 69.
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:ENSSTOP00000010414.3};
OS Ictidomys tridecemlineatus (Thirteen-lined ground squirrel) (Spermophilus
OS tridecemlineatus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Sciuromorpha; Sciuridae;
OC Xerinae; Marmotini; Ictidomys.
OX NCBI_TaxID=43179 {ECO:0000313|Ensembl:ENSSTOP00000010414.3, ECO:0000313|Proteomes:UP000005215};
RN [1] {ECO:0000313|Proteomes:UP000005215}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG The Broad Institute Genome Assembly & Analysis Group;
RG Computational R&D Group;
RG and Sequencing Platform;
RA Di Palma F., Alfoldi J., Johnson J., Berlin A., Gnerre S., Jaffe D.,
RA MacCallum I., Young S., Walker B.J., Lindblad-Toh K.;
RT "The Draft Genome of Spermophilus tridecemlineatus.";
RL Submitted (NOV-2011) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSSTOP00000010414.3}
RP IDENTIFICATION.
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 -!- 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; AGTP01068775; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR STRING; 43179.ENSSTOP00000010414; -.
DR Ensembl; ENSSTOT00000011603.3; ENSSTOP00000010414.3; ENSSTOG00000011582.3.
DR eggNOG; KOG3924; Eukaryota.
DR GeneTree; ENSGT00390000013515; -.
DR HOGENOM; CLU_004082_1_0_1; -.
DR InParanoid; I3MHN1; -.
DR TreeFam; TF106393; -.
DR Proteomes; UP000005215; Unassembled WGS sequence.
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 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:UP000005215};
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..310
FT /note="DOT1"
FT /evidence="ECO:0000259|PROSITE:PS51569"
FT REGION 314..460
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 780..852
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 887..925
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 957..1102
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1140..1236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1284..1415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1577..1618
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 557..629
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 314..329
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 381..406
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 407..422
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 423..460
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 806..822
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 896..918
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 965..983
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 985..999
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1046..1060
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1585..1618
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 116..119
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
FT BINDING 139..148
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
FT BINDING 166
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
FT BINDING 202..203
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000256|PIRSR:PIRSR037123-1"
SQ SEQUENCE 1732 AA; 184616 MW; D1E115C100CE77D3 CRC64;
MLLCLFQDKH 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 ARRRQQRESK SNATTPTKVP ESKAAAPAKV PESKAAGPAE
APRDSGAEEE KAGVTTVKKP SPSKARKKKL NKKGRKMAGR KRGRPKKMNT ANPERKPKKN
QSALDLLHSQ TVSRTGTASS SPQDACRSPH SPFYQLPPSV QRHSPNPLLV APTPPALQKL
LESFKIQYLQ FLAYTKTPQY KANLQQLLDQ EKERNAQLLG TAQQLFGHCQ AQKEEIRRLF
QQKLDELGVK ALTYNDLIQA QKEISAHNQQ LREQSEQLER DNSELRSQSL QLLRARCEEL
KLDWSSLSLE NLRKEKQALR SQISEKQRHC LELQISIVEL EKSQRQQELL QLKSCVPPDD
ALSMHLRGKG TLGRELEAEA SRLHLELDCA RLALPHVSSM SPELSMNGHA TSYELCGALS
RPSSKQNTPQ YLASPLDQEV VPCTPSHSGR PRLEKLSGLA LPDYTRLSPA KIVLRRHLSQ
DHAGPAKMVA SEVHSRAEHA KESSLPCQSP GLSSSMKLSP QDPRPTSPGA LPIAGEKSSE
KSGKERAYGS HGETITSLPI SIPLSTVQPN KLPVSIPLAS VVLPSRAERV RSTPSPVPQP
RDSSSTLEKQ NGANSHGAGS SAGGRGLSLA PTGFYAGSMA ISGALVGSPA PLASGAEPVA
LDEPSSSGSL FTTVGSRSTT PQHPLLMPPR HPGPASPAHP LSASPRLAGA TQCPPPDVGK
GDLPSDSGFS DPESEAKRRI VFTISAGGGS TKQSPSTKHS PLAPGARGDC GQSHGQDSRK
RGRRKRTSAG TPSLSTGVSP KRRALPSVAG LFTQSSGSPL NLSSMVSNIN QPLEITAISS
PENSLKSSPI PYQDHDQPPV LKKERPLSQS NGAHYSPLTS DEEPGSEDEP SSTRIERKIA
TISLESKSPP KTLENGGGLG RKPAPASEPV NSSKWKSTFS PISDIGLAKS ADSPLQASSA
LGQSSLFAFR PAPEEPVTAE AKLATHPRKG FSGSLSGADG LSPGANPPNG LAFSGGLAAD
LSLHGFNDGA SLSHKGPEVA GLSAPLSFPS QRGKEGPSEA NPFLNKRQLE GLGGLKGEGG
PGKEPTEPGL PPCGPTDKAA LPHGSRPSKG RDRELDFKNG HNLFISAATV PPGGLLGGPG
LATAVSSAGS AAPATQAHRP FLGTFAPGPQ FTLGPMSLQA NLGSVAGSSV LQSLFSSVPA
AAGLVHVSSA ATRLTNSHTM GSFSSGVAGG TVGGVFNHTV PSASAHPFGA SVGSGAVCSS
ATLGLSPLQA AASTSASSFQ APASVETRPP PPPPPAPLPP QHLGRPPAGP PVLHAPPPNV
ALPPPAALLA SNPEPMLLQN LASIPANKAF LPSSSATSLQ PANASLSVKL ASLPHKVSRP
SFTVHHQPLP RLALAQATPA IPQASSTGPS AVWVSLGMPP PYAAHLSGVK PR
//
