DOT1L_DROME
ID DOT1L_DROME Reviewed; 1848 AA.
AC Q8INR6; A4V2H8; Q1RKY0; Q9VI22;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-79 specific;
DE EC=2.1.1.360 {ECO:0000269|PubMed:15371351};
DE AltName: Full=DOT1-like protein;
DE Short=dDOT1L;
DE AltName: Full=Histone H3-K79 methyltransferase;
DE Short=H3-K79-HMTase;
DE AltName: Full=Protein grappa;
GN Name=gpp; ORFNames=CG10272;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RC STRAIN=Berkeley;
RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M.,
RA Park S., Wan K.H., Yu C., Celniker S.E.;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=15371351; DOI=10.1534/genetics.104.033191;
RA Shanower G.A., Mueller M., Blanton J.L., Honti V., Gyurkovics H.,
RA Schedl P.;
RT "Characterization of the grappa gene, the Drosophila histone H3 lysine 79
RT methyltransferase.";
RL Genetics 169:173-184(2005).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-491; SER-492; SER-494;
RP SER-1318; SER-1324 AND SER-1325, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
CC -!- FUNCTION: Histone methyltransferase. Methylates 'Lys-79' of histone H3.
CC Required for Polycomb Group (PcG) and trithorax Group (trxG)
CC maintenance of expression. Also involved in telomeric silencing but do
CC not in centric heterochromatin. Probably participates in pairing
CC sensitivity. {ECO:0000269|PubMed:15371351}.
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:0000255|PROSITE-ProRule:PRU00902,
CC ECO:0000269|PubMed:15371351};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15371351}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A; Synonyms=B;
CC IsoId=Q8INR6-1; Sequence=Displayed;
CC Name=C;
CC IsoId=Q8INR6-2; Sequence=VSP_027492, VSP_012312, VSP_012313;
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos, larvae and adults.
CC {ECO:0000269|PubMed:15371351}.
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 -!- MISCELLANEOUS: Was named 'grappa' because the eyes of mutant flies are
CC of a color similar to that of the Italian spirit.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. DOT1 family. {ECO:0000255|PROSITE-ProRule:PRU00902}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABE73251.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AE014297; AAF54122.2; -; Genomic_DNA.
DR EMBL; AE014297; AAN13378.1; -; Genomic_DNA.
DR EMBL; BT025080; ABE73251.1; ALT_FRAME; mRNA.
DR RefSeq; NP_649655.1; NM_141398.4. [Q8INR6-1]
DR RefSeq; NP_731083.1; NM_169142.2. [Q8INR6-1]
DR RefSeq; NP_731084.1; NM_169143.2. [Q8INR6-1]
DR AlphaFoldDB; Q8INR6; -.
DR SMR; Q8INR6; -.
DR BioGRID; 65994; 12.
DR IntAct; Q8INR6; 3.
DR STRING; 7227.FBpp0292801; -.
DR iPTMnet; Q8INR6; -.
DR PaxDb; Q8INR6; -.
DR PRIDE; Q8INR6; -.
DR EnsemblMetazoa; FBtr0303787; FBpp0292799; FBgn0264495. [Q8INR6-1]
DR EnsemblMetazoa; FBtr0303788; FBpp0292800; FBgn0264495. [Q8INR6-1]
DR EnsemblMetazoa; FBtr0303790; FBpp0292802; FBgn0264495. [Q8INR6-1]
DR GeneID; 40793; -.
DR KEGG; dme:Dmel_CG42803; -.
DR UCSC; CG10272-RA; d. melanogaster. [Q8INR6-1]
DR CTD; 40793; -.
DR FlyBase; FBgn0264495; gpp.
DR VEuPathDB; VectorBase:FBgn0264495; -.
DR eggNOG; KOG3924; Eukaryota.
DR GeneTree; ENSGT00390000013515; -.
DR HOGENOM; CLU_001460_1_0_1; -.
DR InParanoid; Q8INR6; -.
DR BioGRID-ORCS; 40793; 0 hits in 1 CRISPR screen.
DR ChiTaRS; gpp; fly.
DR GenomeRNAi; 40793; -.
DR PRO; PR:Q8INR6; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0264495; Expressed in brain and 21 other tissues.
DR ExpressionAtlas; Q8INR6; baseline and differential.
DR Genevisible; Q8INR6; DM.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:GOC.
DR GO; GO:0035097; C:histone methyltransferase complex; IC:UniProtKB.
DR GO; GO:0005634; C:nucleus; IMP:FlyBase.
DR GO; GO:0031151; F:histone methyltransferase activity (H3-K79 specific); IMP:UniProtKB.
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:0045815; P:epigenetic maintenance of chromatin in transcription-competent conformation; IMP:UniProtKB.
DR GO; GO:0031507; P:heterochromatin assembly; IMP:UniProtKB.
DR GO; GO:0034729; P:histone H3-K79 methylation; IMP:FlyBase.
DR GO; GO:0016571; P:histone methylation; IMP:UniProtKB.
DR GO; GO:2000677; P:regulation of transcription regulatory region DNA binding; IBA:GO_Central.
DR GO; GO:0031509; P:subtelomeric heterochromatin assembly; IMP:UniProtKB.
DR Gene3D; 3.40.50.150; -; 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; PTHR21451; 2.
DR Pfam; PF08123; DOT1; 1.
DR PIRSF; PIRSF037123; Histone_H3-K79_MeTrfase_met; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51569; DOT1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromatin regulator; Methyltransferase; Nucleus;
KW Phosphoprotein; Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..1848
FT /note="Histone-lysine N-methyltransferase, H3 lysine-79
FT specific"
FT /id="PRO_0000186090"
FT DOMAIN 19..336
FT /note="DOT1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT REGION 338..537
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 558..593
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 886..908
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 960..996
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1033..1075
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1165..1190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1221..1333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1345..1374
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1432..1463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1486..1508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1529..1559
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1573..1604
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1637..1714
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1731..1757
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 338..366
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 383..410
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 420..489
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 496..523
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 890..906
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1033..1050
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1169..1190
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1236..1259
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1275..1289
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1297..1332
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1531..1550
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1686..1708
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 142..145
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 165..174
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 192
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 228..229
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT MOD_RES 491
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 494
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1318
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1324
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1325
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT VAR_SEQ 430..1253
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_027492"
FT VAR_SEQ 1561..1573
FT /note="LAASLQDHVRARK -> KLPLVFVRRAWTF (in isoform C)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_012312"
FT VAR_SEQ 1574..1848
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_012313"
SQ SEQUENCE 1848 AA; 201284 MW; 7F391ABB35C3C96D CRC64;
MATPQVKDLV LRSPAGSSDV ISFAWPLQIG HGQDKHDNGI DIIDTIKFVC DELPSMSSAF
EETNLHQIDT ACYKTMTGLV DRFNKAVDSI VALEKGTSLP AERLNKFAHP SLLRHILQLV
YNAAVLDPDK LNQYEPFSPE VYGETSYELV QQMLKHVTVS KEDTFIDLGS GVGQVVLQMA
GSFPLKTCIG IEKADTPARY AERMDVIFRQ YMGWFGKRFC EYKLIKGDFL VDEHRENITS
STLVFVNNFA FGPTVDHQLK ERFADLRDGA RVVSSKSFCP LNFRITDRNL SDIGTIMHVS
EIPPLKGSVS WTCKPVSYYL HVIDRTILER YFQRLKTKGG NDHESVGTVR TTRDRAKREA
NVGQHHHNNH HSNNHANSNN HQRDREQSNG ATATAAHQQR HQSQSPANVS GAGIVLAASG
QQAASKTRQQ LQHQHNQQQR SLDMESSTES DGDATNGNGG NTTTATNTTS ASNGPMTRKV
WSDWCSSKGK SSQSDDEENN NSNSNGGSNG GSIGGGSVGR QARATTQKKR KKLTRKAAIA
SKSAAAAQRE AEAAAAAAVS VPSKESSSKE DPPRAASAGP GRKGRMKKGA RGRKSLKIVG
LEALHKQTVL STSLDTMTKK LPAAPGTVDQ QLTALLTENM SHAELDIPTA PQDTPYALQI
LLDVFRSQYT SMIEHMKSSA YVPQVQKQIA QEQERMARLK NRASQLDKQI KVLIDDSVAL
LKVRMNELGI HVNSPNDLIA QAKEIVGRHK DLQHTASRMR NEVTFYEGEQ KLLLNKQLKN
LPEYQKLCGT VNGKVKLEVP PELSETTAQE LVLKEIANTL SQRKKLYAQV STIEQETSVL
QKTAEERSTA ATLLAQGTNM IVSTGSSSSS STTVCASAVT AQSNKLNSVK NSRRNREHRA
RSQEWPEVPE VGKIQESNPE VLAQKIVETC RQIEAGKFQG AGAPSSQVNG KNKAIIEVPP
PPATAPVSIK SSPGHHYKDT TLMPAPKQQQ QQQMTLSQLP KCELPGLSTS RKQESPKVAN
FEDRLKSIIT TALNEDQEQR SKAVESSPSP SPLHSPAPKR SKQHPAGAIN PAQSLPNNLH
NIITVSTQGL MHLNANTTIS PITPPLPGPG AGATASTAPP PPANLPYGAY GGAVAKTTIS
GKYQAAKEPK YSPVRQAPLP PPPSHMASLY PAGQQTTPAD LGYQRRRSSV SATSYEHYMV
QQQQQLQQQQ LMLAAAAHAA QRQQMRVEEQ QQQQQHQHHH HHHHHHPQHR LPQHVQHQHP
HQHHPNEFKA PPADSHLQRS SSREQLIVEP PQTQPLELLP RASSANSDYS GYRIRPPSRP
SSNSSQPDYT QVSPAKMALR RHLSQEKLSQ HVTPQATPPL PGHGGAPTSG KTIGDLVNGE
IERTLEISHQ SIINAAVNMS TSGASFMERA FLNERSNDRL LINLNAQRPE RVHVRPLSEE
SQDPQPTSYA QERGPGLGAG GAAAGGNSNL ATLAHVAYAQ KAQGGARANA GTAPPATHSS
SARSGRDYQP VALPRAELKG SIEAYFHEEQ QQKQSKGAGS AGSSSLRGPR LNGANPPLEG
LAASLQDHVR ARKYKEETEE RQRRAAAAAS SSAGPPAGME LPTHYAHQAP PAHSYHHHGA
SINGTPHKVE LGIKRSSPLA PHQQPPRPSK LAHYEPPTTQ QQHAHAHLYA NGQVLPPPPA
HDATTPSPTP SSSSSSCGRR SNSNNGKLLV DPPLLMSPEI NSLLGDERPL QLSHHQQQQQ
QMLHHHQSQQ QQHLQLTQQQ LRVAHLGHGL SHGHSTMPTL GGQRNGNGNA ADDVNDLATQ
RTITNYDPRR RLRTTLSGPT KLSAAHSNQN LNGYVMADSS SSCPTIPQ
