Q8INR6 (DOT1L_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	gpp
ORF Names:	CG10272

Organism

Drosophila melanogaster (Fruit fly)

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	1848 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.4
Catalytic activity	S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. Ref.4
Subcellular location	Nucleus Ref.4.
Developmental stage	Expressed in embryos, larvae and adults. Ref.4
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.
Sequence similarities	Belongs to the DOT1 family.
Sequence caution	The sequence ABE73251.1 differs from that shown. Reason: Frameshift at position 127.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	S-adenosyl-L-methionine
Molecular function	Chromatin regulator Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	chromatin silencing at telomere Inferred from mutant phenotype Ref.4. Source: UniProtKB chromatin-mediated maintenance of transcription Inferred from mutant phenotype Ref.4. Source: UniProtKB
Cellular component	histone methyltransferase complex Inferred by curator Ref.4. Source: UniProtKB
Molecular function	histone methyltransferase activity (H3-K79 specific) Inferred from mutant phenotype Ref.4. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: Q8INR6-1)

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.

Note: No experimental confirmation available.

Isoform C (identifier: Q8INR6-2)

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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1848	1848	Histone-lysine N-methyltransferase, H3 lysine-79 specific		PRO_0000186090
Regions
	Region	167 – 169	3	S-adenosyl-L-methionine binding By similarity
	Motif	163 – 174	12	SAM-binding motif 1
	Motif	189 – 195	7	SAM-binding motif 2
	Motif	242 – 251	10	SAM-binding motif 3
	Compositional bias	544 – 547	4	Poly-Ala
	Compositional bias	551 – 558	8	Poly-Ala
	Compositional bias	866 – 871	6	Poly-Ser
	Compositional bias	959 – 962	4	Poly-Pro
	Compositional bias	988 – 993	6	Poly-Gln
	Compositional bias	1119 – 1122	4	Poly-Pro
	Compositional bias	1158 – 1163	6	Poly-Pro
	Compositional bias	1201 – 1210	10	Poly-Gln
	Compositional bias	1214 – 1220	7	Poly-Ala
	Compositional bias	1230 – 1235	6	Poly-Gln
	Compositional bias	1236 – 1246	11	Poly-His
	Compositional bias	1585 – 1589	5	Poly-Ala
	Compositional bias	1676 – 1679	4	Poly-Pro
	Compositional bias	1691 – 1696	6	Poly-Ser
	Compositional bias	1736 – 1741	6	Poly-Gln
	Compositional bias	1747 – 1752	6	Poly-Gln
	Compositional bias	1839 – 1842	4	Poly-Ser
Sites
	Binding site	145	1	S-adenosyl-L-methionine By similarity
	Binding site	174	1	S-adenosyl-L-methionine By similarity
	Binding site	192	1	S-adenosyl-L-methionine By similarity
	Binding site	228	1	S-adenosyl-L-methionine By similarity
Amino acid modifications
	Modified residue	491	1	Phosphoserine Ref.5
	Modified residue	492	1	Phosphoserine Ref.5
	Modified residue	494	1	Phosphoserine Ref.5
	Modified residue	1318	1	Phosphoserine Ref.5
	Modified residue	1324	1	Phosphoserine Ref.5
	Modified residue	1325	1	Phosphoserine Ref.5
Natural variations
	Alternative sequence	430 – 1253	824	Missing in isoform C.		VSP_027492
	Alternative sequence	1561 – 1573	13	LAASL…VRARK → KLPLVFVRRAWTF in isoform C.		VSP_012312
	Alternative sequence	1574 – 1848	275	Missing in isoform C.		VSP_012313

Sequences

	Sequence		Length	Mass (Da)
	Isoform A (B) [UniParc]. Last modified December 21, 2004. Version 2. Checksum: 7F391ABB35C3C96D	FASTA	1,848	201,284
	10 20 30 40 50 60 MATPQVKDLV LRSPAGSSDV ISFAWPLQIG HGQDKHDNGI DIIDTIKFVC DELPSMSSAF 70 80 90 100 110 120 EETNLHQIDT ACYKTMTGLV DRFNKAVDSI VALEKGTSLP AERLNKFAHP SLLRHILQLV 130 140 150 160 170 180 YNAAVLDPDK LNQYEPFSPE VYGETSYELV QQMLKHVTVS KEDTFIDLGS GVGQVVLQMA 190 200 210 220 230 240 GSFPLKTCIG IEKADTPARY AERMDVIFRQ YMGWFGKRFC EYKLIKGDFL VDEHRENITS 250 260 270 280 290 300 STLVFVNNFA FGPTVDHQLK ERFADLRDGA RVVSSKSFCP LNFRITDRNL SDIGTIMHVS 310 320 330 340 350 360 EIPPLKGSVS WTCKPVSYYL HVIDRTILER YFQRLKTKGG NDHESVGTVR TTRDRAKREA 370 380 390 400 410 420 NVGQHHHNNH HSNNHANSNN HQRDREQSNG ATATAAHQQR HQSQSPANVS GAGIVLAASG 430 440 450 460 470 480 QQAASKTRQQ LQHQHNQQQR SLDMESSTES DGDATNGNGG NTTTATNTTS ASNGPMTRKV 490 500 510 520 530 540 WSDWCSSKGK SSQSDDEENN NSNSNGGSNG GSIGGGSVGR QARATTQKKR KKLTRKAAIA 550 560 570 580 590 600 SKSAAAAQRE AEAAAAAAVS VPSKESSSKE DPPRAASAGP GRKGRMKKGA RGRKSLKIVG 610 620 630 640 650 660 LEALHKQTVL STSLDTMTKK LPAAPGTVDQ QLTALLTENM SHAELDIPTA PQDTPYALQI 670 680 690 700 710 720 LLDVFRSQYT SMIEHMKSSA YVPQVQKQIA QEQERMARLK NRASQLDKQI KVLIDDSVAL 730 740 750 760 770 780 LKVRMNELGI HVNSPNDLIA QAKEIVGRHK DLQHTASRMR NEVTFYEGEQ KLLLNKQLKN 790 800 810 820 830 840 LPEYQKLCGT VNGKVKLEVP PELSETTAQE LVLKEIANTL SQRKKLYAQV STIEQETSVL 850 860 870 880 890 900 QKTAEERSTA ATLLAQGTNM IVSTGSSSSS STTVCASAVT AQSNKLNSVK NSRRNREHRA 910 920 930 940 950 960 RSQEWPEVPE VGKIQESNPE VLAQKIVETC RQIEAGKFQG AGAPSSQVNG KNKAIIEVPP 970 980 990 1000 1010 1020 PPATAPVSIK SSPGHHYKDT TLMPAPKQQQ QQQMTLSQLP KCELPGLSTS RKQESPKVAN 1030 1040 1050 1060 1070 1080 FEDRLKSIIT TALNEDQEQR SKAVESSPSP SPLHSPAPKR SKQHPAGAIN PAQSLPNNLH 1090 1100 1110 1120 1130 1140 NIITVSTQGL MHLNANTTIS PITPPLPGPG AGATASTAPP PPANLPYGAY GGAVAKTTIS 1150 1160 1170 1180 1190 1200 GKYQAAKEPK YSPVRQAPLP PPPSHMASLY PAGQQTTPAD LGYQRRRSSV SATSYEHYMV 1210 1220 1230 1240 1250 1260 QQQQQLQQQQ LMLAAAAHAA QRQQMRVEEQ QQQQQHQHHH HHHHHHPQHR LPQHVQHQHP 1270 1280 1290 1300 1310 1320 HQHHPNEFKA PPADSHLQRS SSREQLIVEP PQTQPLELLP RASSANSDYS GYRIRPPSRP 1330 1340 1350 1360 1370 1380 SSNSSQPDYT QVSPAKMALR RHLSQEKLSQ HVTPQATPPL PGHGGAPTSG KTIGDLVNGE 1390 1400 1410 1420 1430 1440 IERTLEISHQ SIINAAVNMS TSGASFMERA FLNERSNDRL LINLNAQRPE RVHVRPLSEE 1450 1460 1470 1480 1490 1500 SQDPQPTSYA QERGPGLGAG GAAAGGNSNL ATLAHVAYAQ KAQGGARANA GTAPPATHSS 1510 1520 1530 1540 1550 1560 SARSGRDYQP VALPRAELKG SIEAYFHEEQ QQKQSKGAGS AGSSSLRGPR LNGANPPLEG 1570 1580 1590 1600 1610 1620 LAASLQDHVR ARKYKEETEE RQRRAAAAAS SSAGPPAGME LPTHYAHQAP PAHSYHHHGA 1630 1640 1650 1660 1670 1680 SINGTPHKVE LGIKRSSPLA PHQQPPRPSK LAHYEPPTTQ QQHAHAHLYA NGQVLPPPPA 1690 1700 1710 1720 1730 1740 HDATTPSPTP SSSSSSCGRR SNSNNGKLLV DPPLLMSPEI NSLLGDERPL QLSHHQQQQQ 1750 1760 1770 1780 1790 1800 QMLHHHQSQQ QQHLQLTQQQ LRVAHLGHGL SHGHSTMPTL GGQRNGNGNA ADDVNDLATQ 1810 1820 1830 1840 RTITNYDPRR RLRTTLSGPT KLSAAHSNQN LNGYVMADSS SSCPTIPQ
	Isoform C [UniParc]. Checksum: 6CAB3C7E46B22775	FASTA	749	82,324
	10 20 30 40 50 60 MATPQVKDLV LRSPAGSSDV ISFAWPLQIG HGQDKHDNGI DIIDTIKFVC DELPSMSSAF 70 80 90 100 110 120 EETNLHQIDT ACYKTMTGLV DRFNKAVDSI VALEKGTSLP AERLNKFAHP SLLRHILQLV 130 140 150 160 170 180 YNAAVLDPDK LNQYEPFSPE VYGETSYELV QQMLKHVTVS KEDTFIDLGS GVGQVVLQMA 190 200 210 220 230 240 GSFPLKTCIG IEKADTPARY AERMDVIFRQ YMGWFGKRFC EYKLIKGDFL VDEHRENITS 250 260 270 280 290 300 STLVFVNNFA FGPTVDHQLK ERFADLRDGA RVVSSKSFCP LNFRITDRNL SDIGTIMHVS 310 320 330 340 350 360 EIPPLKGSVS WTCKPVSYYL HVIDRTILER YFQRLKTKGG NDHESVGTVR TTRDRAKREA 370 380 390 400 410 420 NVGQHHHNNH HSNNHANSNN HQRDREQSNG ATATAAHQQR HQSQSPANVS GAGIVLAASG 430 440 450 460 470 480 QQAASKTRQH VQHQHPHQHH PNEFKAPPAD SHLQRSSSRE QLIVEPPQTQ PLELLPRASS 490 500 510 520 530 540 ANSDYSGYRI RPPSRPSSNS SQPDYTQVSP AKMALRRHLS QEKLSQHVTP QATPPLPGHG 550 560 570 580 590 600 GAPTSGKTIG DLVNGEIERT LEISHQSIIN AAVNMSTSGA SFMERAFLNE RSNDRLLINL 610 620 630 640 650 660 NAQRPERVHV RPLSEESQDP QPTSYAQERG PGLGAGGAAA GGNSNLATLA HVAYAQKAQG 670 680 690 700 710 720 GARANAGTAP PATHSSSARS GRDYQPVALP RAELKGSIEA YFHEEQQQKQ SKGAGSAGSS 730 740 SLRGPRLNGA NPPLEGKLPL VFVRRAWTF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[2]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
[3]	Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M., Park S., Wan K.H., Yu C., Celniker S.E. Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C). Strain: Berkeley.
[4]	"Characterization of the grappa gene, the Drosophila histone H3 lysine 79 methyltransferase." Shanower G.A., Mueller M., Blanton J.L., Honti V., Gyurkovics H., Schedl P. Genetics 169:173-184(2005) [PubMed: 15371351] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, ENZYME ACTIVITY, DEVELOPMENTAL STAGE.
[5]	"Phosphoproteome analysis of Drosophila melanogaster embryos." Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P. J. Proteome Res. 7:1675-1682(2008) [PubMed: 18327897] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-491; SER-492; SER-494; SER-1318; SER-1324 AND SER-1325, MASS SPECTROMETRY. Tissue: Embryo.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AE014297 Genomic DNA. Translation: AAF54122.2. AE014297 Genomic DNA. Translation: AAN13378.1. BT025080 mRNA. Translation: ABE73251.1. Frameshift.
RefSeq	NP_649655.1. NM_141398.2. NP_731083.1. NM_169142.2.
3D structure databases
ProteinModelPortal	Q8INR6.
SMR	Q8INR6. Positions 7-338.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-952748.
STRING	Q8INR6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0303787; FBpp0292799; FBgn0261972. FBtr0303788; FBpp0292800; FBgn0261972. FBtr0303790; FBpp0292802; FBgn0261972.
GeneID	40793.
KEGG	dme:Dmel_CG42803.
UCSC	CG10272-RA. d. melanogaster.
Organism-specific databases
CTD	40793.
FlyBase	FBgn0261972. gpp.
Phylogenomic databases
eggNOG	inNOG08916.
GeneTree	EMGT00050000001457.
InParanoid	Q8INR6.
OMA	QVSPAKM.
OrthoDB	EOG4XSJ4Q.
PhylomeDB	Q8INR6.
Gene expression databases
Bgee	Q8INR6.
GermOnline	CG10272. Drosophila melanogaster.
Family and domain databases
InterPro	IPR013110. DOT1. IPR021169. Histone_H3-K79_MeTrfase_met. [Graphical view]
KO	K11427.
Pfam	PF08123. DOT1. 1 hit. [Graphical view]
PIRSF	PIRSF037123. Histone_H3-K79_MeTrfase_met. 1 hit.
ProtoNet	Search...
Other
NextBio	820620.

Entry information

Entry name

DOT1L_DROME

Accession

Primary (citable) accession number: Q8INR6
Secondary accession number(s): A4V2H8, Q1RKY0, Q9VI22

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 21, 2004
Last sequence update:	December 21, 2004
Last modified:	January 25, 2012
This is version 73 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project