DOT11_CAEEL
ID DOT11_CAEEL Reviewed; 946 AA.
AC Q6AW06; A0A061AD87; Q6AW05;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-79 specific {ECO:0000255|RuleBase:RU271113};
DE EC=2.1.1.360 {ECO:0000255|PROSITE-ProRule:PRU00902, ECO:0000305|PubMed:23806335};
DE AltName: Full=Histone H3-K79 methyltransferase {ECO:0000255|RuleBase:RU271113};
GN Name=dot-1.1 {ECO:0000303|PubMed:23806335,
GN ECO:0000312|WormBase:Y39G10AR.18a};
GN ORFNames=Y39G10AR.18 {ECO:0000312|WormBase:Y39G10AR.18a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH ZFP-1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=23806335; DOI=10.1016/j.molcel.2013.06.002;
RA Cecere G., Hoersch S., Jensen M.B., Dixit S., Grishok A.;
RT "The ZFP-1(AF10)/DOT-1 complex opposes H2B ubiquitination to reduce Pol II
RT transcription.";
RL Mol. Cell 50:894-907(2013).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=31088904; DOI=10.1534/g3.119.400328;
RA Rahe D., Hobert O.;
RT "Restriction of cellular plasticity of differentiated cells mediated by
RT chromatin modifiers, transcription factors and protein kinases.";
RL G3 (Bethesda) 7:2287-2302(2019).
CC -!- FUNCTION: Histone methyltransferase, which in complex with zfp-1,
CC methylates 'Lys-79' of histone H3 to activate transcription (Probable).
CC During stress, the zfp-1-dot-1.1 complex also plays a role in the
CC deubiquitination of histone H2B sites, which negatively modulates the
CC RNA polymerase II-induced transcription of highly expressed genes
CC (PubMed:23806335). Involved in controlling tissue-specific gene
CC expression, particularly in the epidermis (PubMed:31088904).
CC {ECO:0000269|PubMed:23806335, ECO:0000269|PubMed:31088904,
CC ECO:0000305|PubMed:23806335}.
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:0000305|PubMed:23806335};
CC -!- SUBUNIT: Interacts with zfp-1 (via C-terminus) to form a heterodimer
CC known as the zfp-1-dot-1.1 complex or DotCom complex.
CC {ECO:0000269|PubMed:23806335}.
CC -!- INTERACTION:
CC Q6AW06; P34447: zfp-1; NbExp=3; IntAct=EBI-21195283, EBI-6740300;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|RuleBase:RU271113,
CC ECO:0000305|PubMed:23806335}. Chromosome {ECO:0000305|PubMed:23806335}.
CC Note=zfp-1 and dot-1.1 colocalize to promoters of highly expressed
CC genes (PubMed:23806335). zfp-1 recruits dot-1.1 (PubMed:23806335).
CC {ECO:0000269|PubMed:23806335}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:Y39G10AR.18a};
CC IsoId=Q6AW06-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:Y39G10AR.18b};
CC IsoId=Q6AW06-2; Sequence=VSP_060336;
CC Name=c {ECO:0000312|WormBase:Y39G10AR.18c};
CC IsoId=Q6AW06-3; Sequence=VSP_060335;
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in the ectopic
CC expression of the neuronal identity-inducing transcription factor che-1
CC in the epidermis. {ECO:0000269|PubMed:31088904}.
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:0000255|RuleBase:RU271113}.
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; BX284601; CCD69916.1; -; Genomic_DNA.
DR EMBL; BX284601; CCD69917.1; -; Genomic_DNA.
DR EMBL; BX284601; CDR32823.1; -; Genomic_DNA.
DR RefSeq; NP_001293323.1; NM_001306394.1.
DR RefSeq; NP_740808.2; NM_170824.3. [Q6AW06-1]
DR RefSeq; NP_740809.2; NM_170825.3. [Q6AW06-2]
DR AlphaFoldDB; Q6AW06; -.
DR SMR; Q6AW06; -.
DR ComplexPortal; CPX-4127; ZFP-1(AF10)/DOT-1 complex.
DR IntAct; Q6AW06; 1.
DR STRING; 6239.Y39G10AR.18a.2; -.
DR EPD; Q6AW06; -.
DR PaxDb; Q6AW06; -.
DR PeptideAtlas; Q6AW06; -.
DR EnsemblMetazoa; Y39G10AR.18a.1; Y39G10AR.18a.1; WBGene00021474. [Q6AW06-1]
DR EnsemblMetazoa; Y39G10AR.18b.1; Y39G10AR.18b.1; WBGene00021474. [Q6AW06-2]
DR EnsemblMetazoa; Y39G10AR.18b.2; Y39G10AR.18b.2; WBGene00021474. [Q6AW06-2]
DR EnsemblMetazoa; Y39G10AR.18c.1; Y39G10AR.18c.1; WBGene00021474. [Q6AW06-3]
DR GeneID; 171797; -.
DR KEGG; cel:CELE_Y39G10AR.18; -.
DR UCSC; Y39G10AR.18a; c. elegans.
DR CTD; 171797; -.
DR WormBase; Y39G10AR.18a; CE38003; WBGene00021474; dot-1.1. [Q6AW06-1]
DR WormBase; Y39G10AR.18b; CE36735; WBGene00021474; dot-1.1. [Q6AW06-2]
DR WormBase; Y39G10AR.18c; CE49789; WBGene00021474; dot-1.1. [Q6AW06-3]
DR eggNOG; KOG3924; Eukaryota.
DR GeneTree; ENSGT00390000013515; -.
DR HOGENOM; CLU_310847_0_0_1; -.
DR InParanoid; Q6AW06; -.
DR OMA; LMLRINT; -.
DR OrthoDB; 649516at2759; -.
DR Reactome; R-CEL-3214841; PKMTs methylate histone lysines.
DR PRO; PR:Q6AW06; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00021474; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005694; C:chromosome; IC:ComplexPortal.
DR GO; GO:0035097; C:histone methyltransferase complex; IDA:ComplexPortal.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0031151; F:histone methyltransferase activity (H3-K79 specific); IBA:GO_Central.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
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:0034729; P:histone H3-K79 methylation; IC:ComplexPortal.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IC:ComplexPortal.
DR GO; GO:2000677; P:regulation of transcription regulatory region DNA binding; IBA:GO_Central.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR025789; DOT1_dom.
DR InterPro; IPR030445; H3-K79_meTrfase.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR21451; PTHR21451; 1.
DR Pfam; PF08123; DOT1; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51569; DOT1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromatin regulator; Chromosome; DNA-binding;
KW Methyltransferase; Nucleus; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..946
FT /note="Histone-lysine N-methyltransferase, H3 lysine-79
FT specific"
FT /id="PRO_0000448083"
FT DOMAIN 54..369
FT /note="DOT1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 368..577
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 849..905
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..406
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..426
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 429..446
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 460..488
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 526..555
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 851..871
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 173..176
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 196..205
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 223
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT BINDING 259..260
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00902"
FT VAR_SEQ 1..583
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_060335"
FT VAR_SEQ 2..409
FT /note="SEADAGARDESPSRTAEEPAAAMRIKEERRSSSVDVVDVGNGELLVLHSIFY
FT QGKTLRLPGNRAHMYPVVFQMIKGVCSLVKQLVVAFPKGWDQNTPSISEIAALTKSFNR
FT VAKPFASNWSGSYNTDTLKEWGEPNCSAEVAKAITTYAYECAVPRPADLNQHYKSFTSE
FT TYGETNPEQLISIIDELNIGPQDVFVDLGSGIGQLVCLTAAYAKCKKSVGIELSQVPSN
FT FAQDLAGYFKKFMSHFGKNHGKFEHIQGDFLNPKFKQLICEEATVIFINNFAFDAALML
FT RINTELLQDLKHGTRIVTTKELGTNKKEITFRSTSDINAISHTTELKTTESAVSWTSSH
FT VKFWLTTIDHTKLIKYYEDQRRRQEVKSSREGSEISDGRDMGLKKRKSQRESSVHPDKL
FT QK -> EISSSKKSSASPSHHGPGALGHPDPPGGAGGEDDVFFGRTTRLMWKAQ (in
FT isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060336"
SQ SEQUENCE 946 AA; 103206 MW; 2D454B1A12E1DB41 CRC64;
MSEADAGARD ESPSRTAEEP AAAMRIKEER RSSSVDVVDV GNGELLVLHS IFYQGKTLRL
PGNRAHMYPV VFQMIKGVCS LVKQLVVAFP KGWDQNTPSI SEIAALTKSF NRVAKPFASN
WSGSYNTDTL KEWGEPNCSA EVAKAITTYA YECAVPRPAD LNQHYKSFTS ETYGETNPEQ
LISIIDELNI GPQDVFVDLG SGIGQLVCLT AAYAKCKKSV GIELSQVPSN FAQDLAGYFK
KFMSHFGKNH GKFEHIQGDF LNPKFKQLIC EEATVIFINN FAFDAALMLR INTELLQDLK
HGTRIVTTKE LGTNKKEITF RSTSDINAIS HTTELKTTES AVSWTSSHVK FWLTTIDHTK
LIKYYEDQRR RQEVKSSREG SEISDGRDMG LKKRKSQRES SVHPDKLQKT EQAAASSHQS
PKWNEPDTDY TPPAKKPKKE KLLREQQDAT PASSHHHGAS SSSGKDREKE KEKKKNKIYE
EKKVKTPKPP KSSSSRYSSE TPTSHHHHHR SNSISHSSDV IRPSQPKATA PPPPLVPAPA
RATASTPPPA PPAARAQSPK REEPLEPPTD LIHHGGGQLD AKTMNALHTI REAATTSAQA
AAIQDAINSV LSQPTEASPS AFGPPLAHLP APVAIYPTPP PPPAPAPAAP QQASAAPAAP
NVMPVCTEIA AEQRHTFMIP PTDPFYNMIV SYYFAMKQFC NQSKTADPEF VGRLRLDIEA
EEARRAELKE SITLTSTQID ELLATGVNTL KSRLDELGMP SVTDVTELLA GSKQIVTQHK
GLTNTVAQME NSVAVEEQKL RLIGGPDAVR YFDEAMSHPN VDIAKLTDLV ITTRPPNFVA
QILLPDDSPT ASIDSKVSPS SSSSRRPRQP KPRANNTAAG AGGGGKRGTS GGRKSDGGGG
GGATEDVELE IRQFVQHALK VDNAVKEKER KARGNFMAAA ADRIPR
