ID DOT1L_DICDI Reviewed; 1845 AA.
AC Q55AX2;
DT 16-NOV-2011, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 2.
DT 24-JAN-2024, entry version 96.
DE RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-79 specific {ECO:0000303|PubMed:21187070};
DE EC=2.1.1.360 {ECO:0000250|UniProtKB:Q04089};
DE AltName: Full=Disruptor of telomeric silencing A {ECO:0000303|PubMed:21187070};
DE AltName: Full=Histone H3-K79 methyltransferase {ECO:0000250|UniProtKB:Q04089};
DE Short=H3-K79-HMTase {ECO:0000250|UniProtKB:Q04089};
DE AltName: Full=SAM domain-containing protein {ECO:0000312|EMBL:EAL71677.2};
GN Name=dotA {ECO:0000312|EMBL:EAL71677.2};
GN Synonyms=dot1 {ECO:0000303|PubMed:21187070},
GN KMT4 {ECO:0000303|PubMed:21187070}; ORFNames=DDB_G0271626;
OS Dictyostelium discoideum (Social amoeba).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1] {ECO:0000312|EMBL:EAL71677.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
RN [2] {ECO:0000312|EMBL:EAL71677.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [3] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RC STRAIN=AX2 {ECO:0000269|PubMed:21187070};
RX PubMed=21187070; DOI=10.1016/j.bbrc.2010.12.101;
RA Muller-Taubenberger A., Bonisch C., Furbringer M., Wittek F., Hake S.B.;
RT "The histone methyltransferase Dot1 is required for DNA damage repair and
RT proper development in Dictyostelium.";
RL Biochem. Biophys. Res. Commun. 404:1016-1022(2011).
CC -!- FUNCTION: Histone methyltransferase that specifically methylates
CC histone H3 to form H3K79me. This methylation is required for telomere
CC silencing, correct growth and development, and for resistance to DNA
CC damage induced by UV LIGHT. {ECO:0000269|PubMed:21187070}.
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:0000250|UniProtKB:Q04089, ECO:0000255|PROSITE-
CC ProRule:PRU00902};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q04089}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the whole life cycle.
CC {ECO:0000269|PubMed:21187070}.
CC -!- DISRUPTION PHENOTYPE: Individuals exhibit 4-5 hours delay in
CC development. Development does progress with fewer fruiting bodies and
CC smaller spore heads. No apparent changes in cell cycle regulation.
CC {ECO:0000269|PubMed:21187070}.
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:0000303|PubMed:21187070}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. DOT1 family. {ECO:0000255|PROSITE-ProRule:PRU00902}.
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DR EMBL; AAFI02000006; EAL71677.2; -; Genomic_DNA.
DR RefSeq; XP_645574.2; XM_640482.2.
DR AlphaFoldDB; Q55AX2; -.
DR SMR; Q55AX2; -.
DR STRING; 44689.Q55AX2; -.
DR PaxDb; 44689-DDB0233511; -.
DR EnsemblProtists; EAL71677; EAL71677; DDB_G0271626.
DR GeneID; 8618027; -.
DR KEGG; ddi:DDB_G0271626; -.
DR dictyBase; DDB_G0271626; dotA.
DR eggNOG; KOG3924; Eukaryota.
DR HOGENOM; CLU_237041_0_0_1; -.
DR InParanoid; Q55AX2; -.
DR PRO; PR:Q55AX2; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0005634; C:nucleus; IDA:dictyBase.
DR GO; GO:0031151; F:histone H3K79 methyltransferase activity; IDA:dictyBase.
DR GO; GO:0140956; F:histone H3K79 trimethyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:0006281; P:DNA repair; IMP:dictyBase.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0031156; P:regulation of sorocarp development; IMP:dictyBase.
DR CDD; cd02440; AdoMet_MTases; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR InterPro; IPR025789; DOT1_dom.
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 SUPFAM; SSF81995; beta-sandwich domain of Sec23/24; 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; DNA damage; DNA repair; Methyltransferase; Nucleus;
KW Reference proteome; Repeat; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN 1..1845
FT /note="Histone-lysine N-methyltransferase, H3 lysine-79
FT specific"
FT /id="PRO_0000413849"
FT DOMAIN 1125..1446
FT /note="DOT1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT REGION 1..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 83..306
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 450..470
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 486..571
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 585..681
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 625..639
FT /note="Required for interaction with nucleosomes and DNA"
FT /evidence="ECO:0000250|UniProtKB:Q04089"
FT REGION 741..767
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 862..881
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 963..1102
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1463..1559
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1610..1661
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1735..1762
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1772..1791
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1799..1845
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 85..176
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 186..266
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 450..464
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 741..762
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 966..1069
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1083..1102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1463..1519
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1520..1534
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1537..1559
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1610..1643
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1741..1758
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1799..1818
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1251..1254
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 1274..1283
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 1300
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q04089,
FT ECO:0000255|PROSITE-ProRule:PRU00902"
SQ SEQUENCE 1845 AA; 212281 MW; 6CDF92C0D67AAD87 CRC64;
MSTNSTPRKQ KLSNSKSLQN SPISPTVKKT NSFPLGNNIP TNINRSKKDK NNNSNNNINN
NNSNGIGSNT IINSTPIATT PVPPLPFIHS SSSSSSSPSP SSSSSSPFPK AKKSPSLSIN
QQQQQQPQQP QQSPQSQQSP QSQQSQQSQQ QQPQQPQEQQ EPLPNLSFLR NQEPDKNVLP
TSRKRPPSVM PSTPNQSSNS SSLNSSLNFS SSNSSPSPTS TQSNNSRFET RSQNDQYENN
NNNNNNNNNN NNNNNNNNNN NNNIECIVID DDDDDDDDEG NSIKSTHTST QSTPIRDRRQ
RDNKWTINPL PQFQREIIDV DTPSPPNESL SIVSQTTTNT ITDTTSIQTP TLIRQSSSLL
SSSSSLSPST TSTPLTQNNI NLQNAQVIAT MTAPMEIELP TIVQLEPLFS SEFTTSTQNL
FIQTPPFTST LTLPTTTAQT SQTLFTIQTS HDINNNNNNN NNNKNKNKNK KEIEKEKEKL
REALKQKLKE YENENEKERE KERKREREIE IERERKERER KEREKERKKE KEREREREER
ERKEIERKER EREEREERER KEIERKETER KEIERKEIER KEIERKERER KERKEREERE
EREREERERK EREEREKEIE MEREKKKEKE KEKEKEKEKE KEKEKEKEKE KEKEKEKEKK
RKENEVENEI EKERREKNDS YMVLNYHHSI DDHHSESESE SDSDQDSIYS ISTQELSSVI
SDNDFCDSDN EKVANNNRTV GETFLNDSRN NNNNNNNNKN NNNKKIENDK NQLIERERLI
SAFNDKAFLY ALDTIREVLG GIDFKLKVSK EQIIEISTNA KKPLNILSEP EQQQQQQQQQ
QQQQHQQQQQ QQQQQQQQQQ QQTTKTTTTT NNTTTTTAET EKPKEVFLLK KPIKIPYGRD
CKKRLIRRFH GTSRNPLFHK NLESTLKLLK RAKFDWASIE FDTKSYLMNC NCKTVCHKSE
RMKDNPTNKL QNNNRNNNNN NNNIINNNNN NNNKNNNNKN NNNKNNNRNN NSIAKKIGTN
NNNNNTTIIK NNNNNNNNNN NNNNNNNNII KNNNNNNKNN NNNNNTIVKK IETIKKDINK
KPTKTTTTTS SSSSSTSSSN SLTVIKKPVK KINGSQRICL FEDDFDVGIG VPVTTGTSET
TTTRASSIRR KMNISNIFDD FTKKPRQNKY NEIEMPDLFA SKECNYTLEQ QAPFIRAQKL
LLTQQHENNL YNGKRFMKYD EWLDLYHGEM RSSIQNPKVL KHYISFSQEV YGEAEPTLLR
HWIHLGLIKP TDVFCDIGCG IGNVLFQLAA QVGCRVIGVE IRKDLYDISQ SMLEIYKKRS
LELGLHPSTQ QIKIYNCDVK GSLEFDFSEP NVFFMHNTCF GPELEISIME LFKKYSKPGT
KVITMKTLCP RFKPSDKKTK PWGIFKYPYE SYEMEEGSLS WRSATNCSFY SFTIDDKDSD
IVTDQTHLNR VILSTPKKKH SKLQLFSSSS LPSSPPSSSS SSSPPNIATN TTTTTTTTTT
TSPSSISLPS PYLSPSKKTP NSNKRDRSDI DNSNSDDGDE NNNNININNN NNNSNNKPIK
LKLSMDHSID NQSNSESSDT DVEYMPWSKR NNRKKRKSLS YSLDSYLSSR ISPSLSLSTS
SSSSSSLDSS PYSSPPSSSS SDNENDDDNG DDEDDSSSSN DTKLKEKLLL MKNNEKIGGA
PPLTRRNANS DTNKLVQGCY QSLSSYALPK EESQIHKLQL QAKLLEHKNS LVLKHQKSIH
DQQKRLSRKQ KKLAKKNKKK EQQLQAQAKT INYNNNNNNN NQNDNQVNHN NLNENEINTD
LINGYNNNNN NNIINNDNDN DNDNDKDDDK DSNNKDYNNI NDNNK
//
