LOCUS       NP_115871               1537 aa            linear   PRI 12-NOV-2024
DEFINITION  histone-lysine N-methyltransferase, H3 lysine-79 specific isoform 1
            [Homo sapiens].
ACCESSION   NP_115871
VERSION     NP_115871.1
DBSOURCE    REFSEQ: accession NM_032482.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 1537)
  AUTHORS   Hu,Y., Ye,S., Kong,J., Zhou,Q., Wang,Z., Zhang,Y., Yan,H., Wang,Y.,
            Li,T., Xie,Y., Chen,B., Zhao,Y., Zhang,T., Zheng,X., Niu,J., Hu,B.,
            Wang,S., Chen,Z. and Zheng,C.
  TITLE     DOT1L protects against podocyte injury in diabetic kidney disease
            through phospholipase C-like 1
  JOURNAL   Cell Commun Signal 22 (1), 519 (2024)
   PUBMED   39456056
  REMARK    GeneRIF: DOT1L protects against podocyte injury in diabetic kidney
            disease through phospholipase C-like 1.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 1537)
  AUTHORS   Kanojia,A., Roy,G., Madhubala,R. and Muthuswami,R.
  TITLE     Interplay between DOT1L and HDAC1 regulates Leishmania donovani
            infection in human THP-1 cells
  JOURNAL   Acta Trop 258, 107352 (2024)
   PUBMED   39103111
  REMARK    GeneRIF: Interplay between DOT1L and HDAC1 regulates Leishmania
            donovani infection in human THP-1 cells.
REFERENCE   3  (residues 1 to 1537)
  AUTHORS   Tang,H., Lu,Y.F., Zeng,R., Liu,C., Shu,Y., Wu,Y., Su,J., Di,L.,
            Qian,J., Zhang,J., Tian,Y., Lu,X., Pei,X.H., Zhu,Q. and Zhu,W.G.
  TITLE     DOT1L-mediated RAP80 methylation promotes BRCA1 recruitment to
            elicit DNA repair
  JOURNAL   Proc Natl Acad Sci U S A 121 (35), e2320804121 (2024)
   PUBMED   39172790
  REMARK    GeneRIF: DOT1L-mediated RAP80 methylation promotes BRCA1
            recruitment to elicit DNA repair.
REFERENCE   4  (residues 1 to 1537)
  AUTHORS   Sudholz,H., Schuster,I.S., Foroutan,M., Sng,X., Andoniou,C.E.,
            Doan,A., Camilleri,T., Shen,Z., Zaph,C., Degli-Esposti,M.A.,
            Huntington,N.D. and Scheer,S.
  TITLE     DOT1L maintains NK cell phenotype and function for optimal tumor
            control
  JOURNAL   Cell Rep 43 (6), 114333 (2024)
   PUBMED   38865244
  REMARK    GeneRIF: DOT1L maintains NK cell phenotype and function for optimal
            tumor control.
REFERENCE   5  (residues 1 to 1537)
  AUTHORS   Adriaanse,F.R.S., Schneider,P., Arentsen-Peters,S.T.C.J.M.,
            Fonseca,A.M.N.D., Stutterheim,J., Pieters,R., Zwaan,C.M. and
            Stam,R.W.
  TITLE     Distinct Responses to Menin Inhibition and Synergy with DOT1L
            Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid
            Leukemia
  JOURNAL   Int J Mol Sci 25 (11), 6020 (2024)
   PUBMED   38892207
  REMARK    GeneRIF: Distinct Responses to Menin Inhibition and Synergy with
            DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and
            Myeloid Leukemia.
            Publication Status: Online-Only
REFERENCE   6  (residues 1 to 1537)
  AUTHORS   Girard,A., Sachidanandam,R., Hannon,G.J. and Carmell,M.A.
  TITLE     A germline-specific class of small RNAs binds mammalian Piwi
            proteins
  JOURNAL   Nature 442 (7099), 199-202 (2006)
   PUBMED   16751776
REFERENCE   7  (residues 1 to 1537)
  AUTHORS   Okada,Y., Feng,Q., Lin,Y., Jiang,Q., Li,Y., Coffield,V.M., Su,L.,
            Xu,G. and Zhang,Y.
  TITLE     hDOT1L links histone methylation to leukemogenesis
  JOURNAL   Cell 121 (2), 167-178 (2005)
   PUBMED   15851025
  REMARK    GeneRIF: mistargeting of hDOT1L to Hoxa9 plays an important role in
            MLL-AF10-mediated leukemogenesis
            Erratum:[Cell. 2005 Jun 3;121(5):809]
REFERENCE   8  (residues 1 to 1537)
  AUTHORS   Min,J., Feng,Q., Li,Z., Zhang,Y. and Xu,R.M.
  TITLE     Structure of the catalytic domain of human DOT1L, a non-SET domain
            nucleosomal histone methyltransferase
  JOURNAL   Cell 112 (5), 711-723 (2003)
   PUBMED   12628190
REFERENCE   9  (residues 1 to 1537)
  AUTHORS   Jikuya,H., Takano,J., Kikuno,R., Hirosawa,M., Nagase,T., Nomura,N.
            and Ohara,O.
  TITLE     Characterization of long cDNA clones from human adult spleen. II.
            The complete sequences of 81 cDNA clones
  JOURNAL   DNA Res 10 (1), 49-57 (2003)
   PUBMED   12693554
REFERENCE   10 (residues 1 to 1537)
  AUTHORS   Feng,Q., Wang,H., Ng,H.H., Erdjument-Bromage,H., Tempst,P.,
            Struhl,K. and Zhang,Y.
  TITLE     Methylation of H3-lysine 79 is mediated by a new family of HMTases
            without a SET domain
  JOURNAL   Curr Biol 12 (12), 1052-1058 (2002)
   PUBMED   12123582
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC005257.1, AF509504.1,
            AC005263.1 and AL080221.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            Summary: The protein encoded by this gene is a histone
            methyltransferase that methylates lysine-79 of histone H3. It is
            inactive against free core histones, but shows significant histone
            methyltransferase activity against nucleosomes. [provided by
            RefSeq, Aug 2011].
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF509504.1, KX792913.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000398665.8/ ENSP00000381657.3
            RefSeq Select criteria :: based on expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..1537
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19p13.3"
     Protein         1..1537
                     /product="histone-lysine N-methyltransferase, H3 lysine-79
                     specific isoform 1"
                     /EC_number="2.1.1.360"
                     /note="histone methyltransferase DOT1L; histone-lysine
                     N-methyltransferase, H3 lysine-79 specific; H3-K79-HMTase;
                     DOT1-like protein; lysine N-methyltransferase 4; histone
                     H3-K79 methyltransferase; DOT1-like, histone H3
                     methyltransferase; DOT1 like histone H3K79
                     methyltransferase; DOT1-like histone methyltransferase"
                     /calculated_mol_wt=164726
     Region          115..317
                     /region_name="DOT1"
                     /note="Histone methylation protein DOT1; pfam08123"
                     /db_xref="CDD:149273"
     Site            order(162..168,186..187,221..223,241)
                     /site_type="other"
                     /note="S-adenosylmethionine binding site [chemical
                     binding]"
                     /db_xref="CDD:100107"
     Region          483..547
                     /region_name="CC_DOT1L"
                     /note="coiled coil domain of disruptor of
                     telomeric-silencing 1-like (DOT1L) and similar proteins;
                     cd20902"
                     /db_xref="CDD:411016"
     Site            order(495,499,507..508,511..512,514..515,518..519,
                     521..522,525..526,529,532..533,536,539..540,543,546..547)
                     /site_type="other"
                     /note="heterodimer interface [polypeptide binding]"
                     /db_xref="CDD:411016"
     Region          511..>661
                     /region_name="COG4372"
                     /note="Uncharacterized protein, contains DUF3084 domain
                     [Function unknown]"
                     /db_xref="CDD:443500"
     Region          775..>1124
                     /region_name="PHA03307"
                     /note="transcriptional regulator ICP4; Provisional"
                     /db_xref="CDD:223039"
     CDS             1..1537
                     /gene="DOT1L"
                     /gene_synonym="DOT1; KMT4"
                     /coded_by="NM_032482.3:253..4866"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS42460.1"
                     /db_xref="GeneID:84444"
                     /db_xref="HGNC:HGNC:24948"
                     /db_xref="MIM:607375"
ORIGIN      
        1 mgeklelrlk spvgaepavy pwplpvydkh hdaaheiiet irwvceeipd lklamenyvl
       61 idydtksfes mqrlcdkynr aidsihqlwk gttqpmklnt rpstgllrhi lqqvynhsvt
      121 dpeklnnyep fspevygets fdlvaqmide ikmtdddlfv dlgsgvgqvv lqvaaatnck
      181 hhygvekadi pakyaetmdr efrkwmkwyg kkhaeytler gdflseewre riantsvifv
      241 nnfafgpevd hqlkerfanm keggrivssk pfaplnfrin srnlsdigti mrvvelsplk
      301 gsvswtgkpv syylhtidrt ilenyfsslk npklreeqea arrrqqresk snaatptkgp
      361 egkvagpada pmdsgaeeek agaatvkkps pskarkkkln kkgrkmagrk rgrpkkmnta
      421 nperkpkknq taldalhaqt vsqtaasspq dayrsphspf yqlppsvqrh spnpllvapt
      481 ppalqklles fkiqylqfla ytktpqykas lqellgqeke knaqllgaaq qllshcqaqk
      541 eeirrlfqqk ldelgvkalt yndliqaqke isahnqqlre qseqleqdnr alrgqslqll
      601 karceelqld watlslekll kekqalksqi sekqrhclel qisiveleks qrqqellqlk
      661 scvppddals lhlrgkgalg relepdasrl hleldctkfs lphlssmspe lsmngqaagy
      721 elcgvlsrps skqntpqyla spldqevvpc tpshvgrprl eklsglaapd ytrlspakiv
      781 lrrhlsqdht vpgrpaasel hsraehtken glpyqspsvp gsmklspqdp rplspgalql
      841 agekssekgl reraygssge litslpisip lstvqpnklp vsiplasvvl psraerarst
      901 pspvlqprdp sstlekqiga nahgagsrsl alapagfsya gsvaisgala gspasltpga
      961 epatldesss sgslfatvgs rsstpqhpll laqprnslpa spahqlsssp rlggaaqgpl
     1021 peaskgdlps dsgfsdpese akrrivftit tgagsakqsp sskhspltas argdcvpshg
     1081 qdsrrrgrrk rasagtpsls agvspkrral psvaglftqp sgsplnlnsm vsninqplei
     1141 taisspetsl ksspvpyqdh dqppvlkker plsqtngahy spltsdeepg sedepssari
     1201 erkiatisle sksppktlen ggglagrkpa pagepvnssk wkstfspisd iglaksadsp
     1261 lqassalsqn slftfrpale epsadaklaa hprkgfpgsl sgadglspgt npangctfgg
     1321 glaadlslhs fsdgaslphk gpeaaglssp lsfpsqrgke gsdanpflsk rqldglaglk
     1381 gegsrgkeag egglplcgpt dktpllsgka akardrevdl knghnlfisa aavppgslls
     1441 gpglapaass aggaassaqt hrsflgpfpp gpqfalgpms lqanlgsvag ssvlqslfss
     1501 vpaaaglvhv ssaatrltns hamgsfsgva ggtvggn
//
