KMT5A_DROME
ID KMT5A_DROME Reviewed; 691 AA.
AC Q9VFK6; Q53ZQ8;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Histone-lysine N-methyltransferase PR-Set7 {ECO:0000303|PubMed:12086618};
DE EC=2.1.1.361 {ECO:0000269|PubMed:12121615};
DE AltName: Full=Lysine N-methyltransferase 5A;
DE AltName: Full=PR/SET domain-containing protein 07;
DE AltName: Full=dSET8 {ECO:0000303|PubMed:12121615};
GN Name=PR-Set7 {ECO:0000303|PubMed:12086618,
GN ECO:0000312|FlyBase:FBgn0011474}; Synonyms=KMT5A;
GN ORFNames=CG3307 {ECO:0000312|FlyBase:FBgn0011474};
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 [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12086618; DOI=10.1016/s1097-2765(02)00548-8;
RA Nishioka K., Rice J.C., Sarma K., Erdjument-Bromage H., Werner J., Wang Y.,
RA Chuikov S., Valenzuela P., Tempst P., Steward R., Lis J.T., Allis C.D.,
RA Reinberg D.;
RT "PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20
RT of histone H4 and is associated with silent chromatin.";
RL Mol. Cell 9:1201-1213(2002).
RN [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=12121615; DOI=10.1016/s0960-9822(02)00924-7;
RA Fang J., Feng Q., Ketel C.S., Wang H., Cao R., Xia L.,
RA Erdjument-Bromage H., Tempst P., Simon J.A., Zhang Y.;
RT "Purification and functional characterization of SET8, a nucleosomal
RT histone H4-lysine 20-specific methyltransferase.";
RL Curr. Biol. 12:1086-1099(2002).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=15681608; DOI=10.1101/gad.1263005;
RA Karachentsev D., Sarma K., Reinberg D., Steward R.;
RT "PR-Set7-dependent methylation of histone H4 Lys 20 functions in repression
RT of gene expression and is essential for mitosis.";
RL Genes Dev. 19:431-435(2005).
RN [7]
RP FUNCTION.
RX PubMed=17227890; DOI=10.1083/jcb.200607178;
RA Sakaguchi A., Steward R.;
RT "Aberrant monomethylation of histone H4 lysine 20 activates the DNA damage
RT checkpoint in Drosophila melanogaster.";
RL J. Cell Biol. 176:155-162(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-195; SER-250; THR-252;
RP SER-281; THR-344; SER-346; SER-383; SER-388 AND SER-392, AND IDENTIFICATION
RP 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 that specifically monomethylates
CC 'Lys-20' of histone H4. H4 'Lys-20' monomethylation is enriched during
CC mitosis and represents a specific tag for epigenetic transcriptional
CC repression. Mainly functions in euchromatin regions, thereby playing a
CC central role in the silencing of euchromatic genes. Required for cell
CC proliferation, possibly by contributing to the maintenance of proper
CC higher-order structure of DNA and chromosome condensation during
CC mitosis. {ECO:0000269|PubMed:12086618, ECO:0000269|PubMed:12121615,
CC ECO:0000269|PubMed:15681608, ECO:0000269|PubMed:17227890}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:60344, Rhea:RHEA-COMP:15554, Rhea:RHEA-COMP:15555,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.361;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00904,
CC ECO:0000269|PubMed:12121615};
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Specifically localizes
CC to mitotic chromosomes. Associates to chromatin-dense and
CC transcriptionally silent euchromatic regions.
CC -!- DEVELOPMENTAL STAGE: Present in ovary, early embryos and throughout the
CC development (at protein level). Deposed in the egg during oogenesis.
CC {ECO:0000269|PubMed:15681608}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family. PR/SET subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00904}.
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DR EMBL; AY283060; AAP35083.1; -; mRNA.
DR EMBL; AE014297; AAF55047.2; -; Genomic_DNA.
DR EMBL; AE014297; AAN13605.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN13606.1; -; Genomic_DNA.
DR EMBL; AY102673; AAM27502.1; -; mRNA.
DR RefSeq; NP_001247100.1; NM_001260171.2.
DR RefSeq; NP_650354.1; NM_142097.4.
DR RefSeq; NP_731900.1; NM_169577.3.
DR AlphaFoldDB; Q9VFK6; -.
DR SMR; Q9VFK6; -.
DR BioGRID; 66819; 11.
DR IntAct; Q9VFK6; 2.
DR MINT; Q9VFK6; -.
DR STRING; 7227.FBpp0082387; -.
DR BindingDB; Q9VFK6; -.
DR ChEMBL; CHEMBL2169717; -.
DR iPTMnet; Q9VFK6; -.
DR PaxDb; Q9VFK6; -.
DR DNASU; 41743; -.
DR EnsemblMetazoa; FBtr0082929; FBpp0082388; FBgn0011474.
DR EnsemblMetazoa; FBtr0082930; FBpp0082389; FBgn0011474.
DR EnsemblMetazoa; FBtr0309996; FBpp0301702; FBgn0011474.
DR GeneID; 41743; -.
DR KEGG; dme:Dmel_CG3307; -.
DR UCSC; CG3307-RA; d. melanogaster.
DR CTD; 41743; -.
DR FlyBase; FBgn0011474; PR-Set7.
DR VEuPathDB; VectorBase:FBgn0011474; -.
DR eggNOG; KOG1085; Eukaryota.
DR GeneTree; ENSGT00940000163293; -.
DR HOGENOM; CLU_025411_0_0_1; -.
DR InParanoid; Q9VFK6; -.
DR OMA; HRILCPS; -.
DR OrthoDB; 362367at2759; -.
DR PhylomeDB; Q9VFK6; -.
DR BRENDA; 2.1.1.361; 1994.
DR Reactome; R-DME-6804760; Regulation of TP53 Activity through Methylation.
DR BioGRID-ORCS; 41743; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 41743; -.
DR PRO; PR:Q9VFK6; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0011474; Expressed in egg cell and 42 other tissues.
DR ExpressionAtlas; Q9VFK6; baseline and differential.
DR Genevisible; Q9VFK6; DM.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005700; C:polytene chromosome; IDA:FlyBase.
DR GO; GO:0042799; F:histone methyltransferase activity (H4-K20 specific); IMP:FlyBase.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0030261; P:chromosome condensation; IDA:FlyBase.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IDA:FlyBase.
DR GO; GO:0034771; P:histone H4-K20 monomethylation; IMP:FlyBase.
DR GO; GO:0016571; P:histone methylation; IMP:FlyBase.
DR GO; GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR016858; Hist_H4-K20_MeTrfase.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS51571; SAM_MT43_PR_SET; 1.
DR PROSITE; PS50280; SET; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Chromatin regulator; Chromosome;
KW Methyltransferase; Mitosis; Nucleus; Phosphoprotein; Reference proteome;
KW Repressor; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN 1..691
FT /note="Histone-lysine N-methyltransferase PR-Set7"
FT /id="PRO_0000186082"
FT DOMAIN 555..676
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 341..363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 382..401
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 407..437
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 464..516
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 415..437
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 565..567
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00904"
FT BINDING 610
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190,
FT ECO:0000255|PROSITE-ProRule:PRU00904"
FT BINDING 637..638
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00904"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 252
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 344
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 388
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
SQ SEQUENCE 691 AA; 76493 MW; 3462A761ED44A2D1 CRC64;
MIMVRRRQRP AKEAASSSSG GASSGSGIPV DQALPLNVAG NLLEDQYFAS PKRKDCRLMK
VTQNGQLPEA TMMAHNKDNK AGRTIGVPLA TRSQTRTIEN FFKANAAAKD SQKTIHTEEQ
LNLGNQELKL DDEELNGQIK LDDEVLKLAD KQINENLPFA DEVDAKAEQK LMDEELQQVV
EELLFDGSSR ASSNSPFYQH DMDVMQEIQQ TPEIPHIKKV TEPLEGLGSL ADFQTHRSAL
RDSHSSTHSS STDNIFLQEP VLTLDIDRTP TKASSIKINR SFELAGAVFS SPPSVLNACL
NGRFNQIVSL NGQKEALDLP HFDLDQHDSS SCDSGVACGL TANTESPAGQ PRRRKPATPH
RILCPSPIKT ALKVTGGICK VGSADPLSPR KSPRKLPTTT AAVAACKSRR RLNQPKPQAP
YQPQLQKPPS QQQQQQQDDI VVVLDDDDDE GDDEDDVRAL IKAAEERENQ NKAPATANSN
KAGMKTMLKP APVKSKTKSK GPTKGQPPLP LAATNGNREM TDFFPVRRSV RKTKTAVKEE
WMRGLEQAVL EERCDGLQVR HFMGKGRGVV ADRPFKRNEF VVEYVGDLIS IGEAAEREKR
YALDENAGCY MYYFKHKSQQ YCIDATVDTG KLGRLINHSR AGNLMTKVVL IKQRPHLVLL
AKDDIEPGEE LTYDYGDRSK ESLLHHPWLA F
