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Protein

Histone-lysine N-methyltransferase, H3 lysine-79 specific

Gene

gpp

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Histone methyltransferase. Methylates 'Lys-79' of histone H3. Required for Polycomb Group (PcG) and trithorax Group (trxG) maintenance of expression. Also involved in telomeric silencing but do not in centric heterochromatin. Probably participates in pairing sensitivity.1 Publication

Catalytic activityi

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].PROSITE-ProRule annotation1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei192 – 1921S-adenosyl-L-methioninePROSITE-ProRule annotation

GO - Molecular functioni

  • histone methyltransferase activity (H3-K79 specific) Source: UniProtKB

GO - Biological processi

  • chromatin-mediated maintenance of transcription Source: UniProtKB
  • chromatin silencing Source: UniProtKB
  • chromatin silencing at telomere Source: UniProtKB
  • histone H3-K79 methylation Source: FlyBase
  • histone methylation Source: UniProtKB
  • lateral inhibition Source: FlyBase
  • positive regulation of gene silencing by miRNA Source: FlyBase
  • regulation of cell cycle Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Transferase

Keywords - Ligandi

S-adenosyl-L-methionine

Enzyme and pathway databases

ReactomeiR-DME-3214841. PKMTs methylate histone lysines.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone-lysine N-methyltransferase, H3 lysine-79 specific (EC:2.1.1.43)
Alternative name(s):
DOT1-like protein
Short name:
dDOT1L
Histone H3-K79 methyltransferase
Short name:
H3-K79-HMTase
Protein grappa
Gene namesi
Name:gpp
ORF Names:CG10272
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 3R

Organism-specific databases

FlyBaseiFBgn0264495. gpp.

Subcellular locationi

GO - Cellular componenti

  • chromosome, telomeric region Source: GOC
  • histone methyltransferase complex Source: UniProtKB
  • nucleus Source: FlyBase
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 18481848Histone-lysine N-methyltransferase, H3 lysine-79 specificPRO_0000186090Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei491 – 4911Phosphoserine1 Publication
Modified residuei492 – 4921Phosphoserine1 Publication
Modified residuei494 – 4941Phosphoserine1 Publication
Modified residuei1318 – 13181Phosphoserine1 Publication
Modified residuei1324 – 13241Phosphoserine1 Publication
Modified residuei1325 – 13251Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ8INR6.

PTM databases

iPTMnetiQ8INR6.

Expressioni

Developmental stagei

Expressed in embryos, larvae and adults.1 Publication

Gene expression databases

BgeeiFBgn0264495.
ExpressionAtlasiQ8INR6. differential.
GenevisibleiQ8INR6. DM.

Interactioni

Protein-protein interaction databases

BioGridi65994. 4 interactions.
IntActiQ8INR6. 3 interactions.
MINTiMINT-952748.
STRINGi7227.FBpp0292801.

Structurei

3D structure databases

ProteinModelPortaliQ8INR6.
SMRiQ8INR6. Positions 8-336.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini19 – 336318DOT1PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni142 – 1454S-adenosyl-L-methionine bindingPROSITE-ProRule annotation
Regioni165 – 17410S-adenosyl-L-methionine bindingPROSITE-ProRule annotation
Regioni228 – 2292S-adenosyl-L-methionine bindingPROSITE-ProRule annotation

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi544 – 5474Poly-Ala
Compositional biasi551 – 5588Poly-Ala
Compositional biasi866 – 8716Poly-Ser
Compositional biasi959 – 9624Poly-Pro
Compositional biasi988 – 9936Poly-Gln
Compositional biasi1119 – 11224Poly-Pro
Compositional biasi1158 – 11636Poly-Pro
Compositional biasi1201 – 121010Poly-Gln
Compositional biasi1214 – 12207Poly-Ala
Compositional biasi1230 – 12356Poly-Gln
Compositional biasi1236 – 124611Poly-HisAdd
BLAST
Compositional biasi1585 – 15895Poly-Ala
Compositional biasi1676 – 16794Poly-Pro
Compositional biasi1691 – 16966Poly-Ser
Compositional biasi1736 – 17416Poly-Gln
Compositional biasi1747 – 17526Poly-Gln
Compositional biasi1839 – 18424Poly-Ser

Sequence similaritiesi

Belongs to the class I-like SAM-binding methyltransferase superfamily. DOT1 family.PROSITE-ProRule annotation
Contains 1 DOT1 domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3924. Eukaryota.
ENOG410XSYC. LUCA.
GeneTreeiENSGT00390000013515.
InParanoidiQ8INR6.
KOiK11427.
OrthoDBiEOG091G00FV.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025789. DOT1_dom.
IPR021169. DOT1L/grappa.
IPR030445. H3-K79_meTrfase.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR21451. PTHR21451. 6 hits.
PfamiPF08123. DOT1. 1 hit.
[Graphical view]
PIRSFiPIRSF037123. Histone_H3-K79_MeTrfase_met. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51569. DOT1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform A (identifier: Q8INR6-1) [UniParc]FASTAAdd to basket
Also known as: B

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MATPQVKDLV LRSPAGSSDV ISFAWPLQIG HGQDKHDNGI DIIDTIKFVC
60 70 80 90 100
DELPSMSSAF EETNLHQIDT ACYKTMTGLV DRFNKAVDSI VALEKGTSLP
110 120 130 140 150
AERLNKFAHP SLLRHILQLV YNAAVLDPDK LNQYEPFSPE VYGETSYELV
160 170 180 190 200
QQMLKHVTVS KEDTFIDLGS GVGQVVLQMA GSFPLKTCIG IEKADTPARY
210 220 230 240 250
AERMDVIFRQ YMGWFGKRFC EYKLIKGDFL VDEHRENITS STLVFVNNFA
260 270 280 290 300
FGPTVDHQLK ERFADLRDGA RVVSSKSFCP LNFRITDRNL SDIGTIMHVS
310 320 330 340 350
EIPPLKGSVS WTCKPVSYYL HVIDRTILER YFQRLKTKGG NDHESVGTVR
360 370 380 390 400
TTRDRAKREA NVGQHHHNNH HSNNHANSNN HQRDREQSNG ATATAAHQQR
410 420 430 440 450
HQSQSPANVS GAGIVLAASG QQAASKTRQQ LQHQHNQQQR SLDMESSTES
460 470 480 490 500
DGDATNGNGG NTTTATNTTS ASNGPMTRKV WSDWCSSKGK SSQSDDEENN
510 520 530 540 550
NSNSNGGSNG GSIGGGSVGR QARATTQKKR KKLTRKAAIA SKSAAAAQRE
560 570 580 590 600
AEAAAAAAVS VPSKESSSKE DPPRAASAGP GRKGRMKKGA RGRKSLKIVG
610 620 630 640 650
LEALHKQTVL STSLDTMTKK LPAAPGTVDQ QLTALLTENM SHAELDIPTA
660 670 680 690 700
PQDTPYALQI LLDVFRSQYT SMIEHMKSSA YVPQVQKQIA QEQERMARLK
710 720 730 740 750
NRASQLDKQI KVLIDDSVAL LKVRMNELGI HVNSPNDLIA QAKEIVGRHK
760 770 780 790 800
DLQHTASRMR NEVTFYEGEQ KLLLNKQLKN LPEYQKLCGT VNGKVKLEVP
810 820 830 840 850
PELSETTAQE LVLKEIANTL SQRKKLYAQV STIEQETSVL QKTAEERSTA
860 870 880 890 900
ATLLAQGTNM IVSTGSSSSS STTVCASAVT AQSNKLNSVK NSRRNREHRA
910 920 930 940 950
RSQEWPEVPE VGKIQESNPE VLAQKIVETC RQIEAGKFQG AGAPSSQVNG
960 970 980 990 1000
KNKAIIEVPP PPATAPVSIK SSPGHHYKDT TLMPAPKQQQ QQQMTLSQLP
1010 1020 1030 1040 1050
KCELPGLSTS RKQESPKVAN FEDRLKSIIT TALNEDQEQR SKAVESSPSP
1060 1070 1080 1090 1100
SPLHSPAPKR SKQHPAGAIN PAQSLPNNLH NIITVSTQGL MHLNANTTIS
1110 1120 1130 1140 1150
PITPPLPGPG AGATASTAPP PPANLPYGAY GGAVAKTTIS GKYQAAKEPK
1160 1170 1180 1190 1200
YSPVRQAPLP PPPSHMASLY PAGQQTTPAD LGYQRRRSSV SATSYEHYMV
1210 1220 1230 1240 1250
QQQQQLQQQQ LMLAAAAHAA QRQQMRVEEQ QQQQQHQHHH HHHHHHPQHR
1260 1270 1280 1290 1300
LPQHVQHQHP HQHHPNEFKA PPADSHLQRS SSREQLIVEP PQTQPLELLP
1310 1320 1330 1340 1350
RASSANSDYS GYRIRPPSRP SSNSSQPDYT QVSPAKMALR RHLSQEKLSQ
1360 1370 1380 1390 1400
HVTPQATPPL PGHGGAPTSG KTIGDLVNGE IERTLEISHQ SIINAAVNMS
1410 1420 1430 1440 1450
TSGASFMERA FLNERSNDRL LINLNAQRPE RVHVRPLSEE SQDPQPTSYA
1460 1470 1480 1490 1500
QERGPGLGAG GAAAGGNSNL ATLAHVAYAQ KAQGGARANA GTAPPATHSS
1510 1520 1530 1540 1550
SARSGRDYQP VALPRAELKG SIEAYFHEEQ QQKQSKGAGS AGSSSLRGPR
1560 1570 1580 1590 1600
LNGANPPLEG LAASLQDHVR ARKYKEETEE RQRRAAAAAS SSAGPPAGME
1610 1620 1630 1640 1650
LPTHYAHQAP PAHSYHHHGA SINGTPHKVE LGIKRSSPLA PHQQPPRPSK
1660 1670 1680 1690 1700
LAHYEPPTTQ QQHAHAHLYA NGQVLPPPPA HDATTPSPTP SSSSSSCGRR
1710 1720 1730 1740 1750
SNSNNGKLLV DPPLLMSPEI NSLLGDERPL QLSHHQQQQQ QMLHHHQSQQ
1760 1770 1780 1790 1800
QQHLQLTQQQ LRVAHLGHGL SHGHSTMPTL GGQRNGNGNA ADDVNDLATQ
1810 1820 1830 1840
RTITNYDPRR RLRTTLSGPT KLSAAHSNQN LNGYVMADSS SSCPTIPQ
Note: No experimental confirmation available.
Length:1,848
Mass (Da):201,284
Last modified:December 21, 2004 - v2
Checksum:i7F391ABB35C3C96D
GO
Isoform C (identifier: Q8INR6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     430-1253: Missing.
     1561-1573: LAASLQDHVRARK → KLPLVFVRRAWTF
     1574-1848: Missing.

Note: No experimental confirmation available.
Show »
Length:749
Mass (Da):82,324
Checksum:i6CAB3C7E46B22775
GO

Sequence cautioni

The sequence ABE73251 differs from that shown. Reason: Frameshift at position 127. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei430 – 1253824Missing in isoform C. 1 PublicationVSP_027492Add
BLAST
Alternative sequencei1561 – 157313LAASL…VRARK → KLPLVFVRRAWTF in isoform C. 1 PublicationVSP_012312Add
BLAST
Alternative sequencei1574 – 1848275Missing in isoform C. 1 PublicationVSP_012313Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AE014297 Genomic DNA. Translation: AAF54122.2.
AE014297 Genomic DNA. Translation: AAN13378.1.
BT025080 mRNA. Translation: ABE73251.1. Frameshift.
RefSeqiNP_649655.1. NM_141398.4. [Q8INR6-1]
NP_731083.1. NM_169142.2. [Q8INR6-1]
NP_731084.1. NM_169143.2. [Q8INR6-1]
UniGeneiDm.20383.

Genome annotation databases

EnsemblMetazoaiFBtr0303787; FBpp0292799; FBgn0264495. [Q8INR6-1]
FBtr0303788; FBpp0292800; FBgn0264495. [Q8INR6-1]
FBtr0303790; FBpp0292802; FBgn0264495. [Q8INR6-1]
GeneIDi40793.
KEGGidme:Dmel_CG42803.
UCSCiCG10272-RA. d. melanogaster. [Q8INR6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AE014297 Genomic DNA. Translation: AAF54122.2.
AE014297 Genomic DNA. Translation: AAN13378.1.
BT025080 mRNA. Translation: ABE73251.1. Frameshift.
RefSeqiNP_649655.1. NM_141398.4. [Q8INR6-1]
NP_731083.1. NM_169142.2. [Q8INR6-1]
NP_731084.1. NM_169143.2. [Q8INR6-1]
UniGeneiDm.20383.

3D structure databases

ProteinModelPortaliQ8INR6.
SMRiQ8INR6. Positions 8-336.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi65994. 4 interactions.
IntActiQ8INR6. 3 interactions.
MINTiMINT-952748.
STRINGi7227.FBpp0292801.

PTM databases

iPTMnetiQ8INR6.

Proteomic databases

PaxDbiQ8INR6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0303787; FBpp0292799; FBgn0264495. [Q8INR6-1]
FBtr0303788; FBpp0292800; FBgn0264495. [Q8INR6-1]
FBtr0303790; FBpp0292802; FBgn0264495. [Q8INR6-1]
GeneIDi40793.
KEGGidme:Dmel_CG42803.
UCSCiCG10272-RA. d. melanogaster. [Q8INR6-1]

Organism-specific databases

CTDi40793.
FlyBaseiFBgn0264495. gpp.

Phylogenomic databases

eggNOGiKOG3924. Eukaryota.
ENOG410XSYC. LUCA.
GeneTreeiENSGT00390000013515.
InParanoidiQ8INR6.
KOiK11427.
OrthoDBiEOG091G00FV.

Enzyme and pathway databases

ReactomeiR-DME-3214841. PKMTs methylate histone lysines.

Miscellaneous databases

ChiTaRSigpp. fly.
GenomeRNAii40793.
PROiQ8INR6.

Gene expression databases

BgeeiFBgn0264495.
ExpressionAtlasiQ8INR6. differential.
GenevisibleiQ8INR6. DM.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025789. DOT1_dom.
IPR021169. DOT1L/grappa.
IPR030445. H3-K79_meTrfase.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR21451. PTHR21451. 6 hits.
PfamiPF08123. DOT1. 1 hit.
[Graphical view]
PIRSFiPIRSF037123. Histone_H3-K79_MeTrfase_met. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51569. DOT1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDOT1L_DROME
AccessioniPrimary (citable) accession number: Q8INR6
Secondary accession number(s): A4V2H8, Q1RKY0, Q9VI22
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: December 21, 2004
Last modified: September 7, 2016
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Miscellaneous

In contrast to other lysine histone methyltransferases, it does not contain a SET domain, suggesting the existence of another mechanism for methylation of lysine residues of histones.
Was named 'grappa' because the eyes of mutant flies are of a color similar to that of the Italian spirit.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.