KMT5A_MOUSE
ID KMT5A_MOUSE Reviewed; 349 AA.
AC Q2YDW7; Q8C0J9;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=N-lysine methyltransferase KMT5A {ECO:0000305};
DE EC=2.1.1.- {ECO:0000250|UniProtKB:Q9NQR1};
DE AltName: Full=H4-K20-HMTase KMT5A;
DE AltName: Full=Histone-lysine N-methyltransferase KMT5A;
DE EC=2.1.1.361 {ECO:0000250|UniProtKB:Q9NQR1};
DE AltName: Full=Lysine-specific methylase 5A {ECO:0000250|UniProtKB:Q9NQR1};
DE AltName: Full=PR/SET domain-containing protein 07;
DE Short=PR-Set7;
DE Short=PR/SET07;
DE AltName: Full=SET domain-containing protein 8;
GN Name=Kmt5a {ECO:0000250|UniProtKB:Q9NQR1}; Synonyms=Setd8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NMRI; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-138, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=23468428; DOI=10.1101/gad.211342.112;
RA Serrano L., Martinez-Redondo P., Marazuela-Duque A., Vazquez B.N.,
RA Dooley S.J., Voigt P., Beck D.B., Kane-Goldsmith N., Tong Q., Rabanal R.M.,
RA Fondevila D., Munoz P., Kruger M., Tischfield J.A., Vaquero A.;
RT "The tumor suppressor SirT2 regulates cell cycle progression and genome
RT stability by modulating the mitotic deposition of H4K20 methylation.";
RL Genes Dev. 27:639-653(2013).
CC -!- FUNCTION: Protein-lysine N-methyltransferase that monomethylates both
CC histones and non-histone proteins. Specifically monomethylates 'Lys-20'
CC of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and
CC represents a specific tag for epigenetic transcriptional repression.
CC Mainly functions in euchromatin regions, thereby playing a central role
CC in the silencing of euchromatic genes. Required for cell proliferation,
CC probably by contributing to the maintenance of proper higher-order
CC structure of DNA during mitosis. Involved in chromosome condensation
CC and proper cytokinesis. Nucleosomes are preferred as substrate compared
CC to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382',
CC leading to repress p53/TP53-target genes. Plays a negative role in TGF-
CC beta response regulation and a positive role in cell migration.
CC {ECO:0000250|UniProtKB:Q9NQR1}.
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:0000250|UniProtKB:Q9NQR1, ECO:0000255|PROSITE-
CC ProRule:PRU00904};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6)-
CC methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:51736, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13053,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929;
CC Evidence={ECO:0000250|UniProtKB:Q9NQR1};
CC -!- SUBUNIT: Interacts with L3MBTL1. Interacts with SIRT2 (phosphorylated
CC form); the interaction is direct, stimulates KMT5A-mediated
CC methyltransferase activity at histone H4 'Lys-20' (H4K20me1) and is
CC increased in a H(2)O(2)-induced oxidative stress-dependent manner (By
CC similarity). {ECO:0000250|UniProtKB:Q9NQR1}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9NQR1}.
CC Chromosome {ECO:0000269|PubMed:23468428}. Note=Specifically localizes
CC to mitotic chromosomes. Associates with silent chromatin on euchromatic
CC arms. Not associated with constitutive heterochromatin (By similarity).
CC Colocalized with SIRT2 at mitotic foci. Associates with chromosomes
CC during mitosis; association is increased in a H(2)O(2)-induced
CC oxidative stress-dependent manner. {ECO:0000250|UniProtKB:Q9NQR1,
CC ECO:0000269|PubMed:23468428}.
CC -!- DOMAIN: Although the SET domain contains the active site of enzymatic
CC activity, both sequences upstream and downstream of the SET domain are
CC required for methyltransferase activity.
CC {ECO:0000250|UniProtKB:Q9NQR1}.
CC -!- PTM: Acetylated at Lys-129; does not change methyltransferase activity.
CC Deacetylated at Lys-129 by SIRT2; does not change methyltransferase
CC activity (By similarity). {ECO:0000250|UniProtKB:Q9NQR1}.
CC -!- PTM: Ubiquitinated and degraded by the DCX(DTL) complex. {ECO:0000305}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC27178.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK030904; BAC27178.1; ALT_FRAME; mRNA.
DR EMBL; BC108333; AAI08334.1; -; mRNA.
DR RefSeq; NP_001297652.1; NM_001310723.1.
DR RefSeq; NP_001297656.1; NM_001310727.1.
DR RefSeq; NP_084517.2; NM_030241.3.
DR AlphaFoldDB; Q2YDW7; -.
DR SMR; Q2YDW7; -.
DR BioGRID; 212564; 2.
DR IntAct; Q2YDW7; 1.
DR STRING; 10090.ENSMUSP00000052953; -.
DR iPTMnet; Q2YDW7; -.
DR PhosphoSitePlus; Q2YDW7; -.
DR MaxQB; Q2YDW7; -.
DR PaxDb; Q2YDW7; -.
DR PRIDE; Q2YDW7; -.
DR ProteomicsDB; 264787; -.
DR GeneID; 67956; -.
DR KEGG; mmu:67956; -.
DR CTD; 387893; -.
DR MGI; MGI:1915206; Kmt5a.
DR eggNOG; KOG1085; Eukaryota.
DR InParanoid; Q2YDW7; -.
DR OrthoDB; 1460495at2759; -.
DR Reactome; R-MMU-2299718; Condensation of Prophase Chromosomes.
DR Reactome; R-MMU-3214841; PKMTs methylate histone lysines.
DR Reactome; R-MMU-6804760; Regulation of TP53 Activity through Methylation.
DR BioGRID-ORCS; 67956; 18 hits in 76 CRISPR screens.
DR ChiTaRS; Kmt5a; mouse.
DR PRO; PR:Q2YDW7; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q2YDW7; protein.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005700; C:polytene chromosome; IBA:GO_Central.
DR GO; GO:0042799; F:histone methyltransferase activity (H4-K20 specific); IBA:GO_Central.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0002039; F:p53 binding; ISS:UniProtKB.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:MGI.
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:0034771; P:histone H4-K20 monomethylation; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0018026; P:peptidyl-lysine monomethylation; ISS:UniProtKB.
DR GO; GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; ISS:UniProtKB.
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 PIRSF; PIRSF027717; Histone_H4-K20_mtfrase; 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 Acetylation; 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; Ubl conjugation.
FT CHAIN 1..349
FT /note="N-lysine methyltransferase KMT5A"
FT /id="PRO_0000228689"
FT DOMAIN 213..334
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT REGION 18..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 65..207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 87..101
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 159..173
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 183..207
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 223..225
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00904"
FT BINDING 268
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 295..296
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00904"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NQR1"
FT MOD_RES 129
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9NQR1"
FT MOD_RES 138
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 204
FT /note="N -> ID (in Ref. 1; BAC27178)"
FT /evidence="ECO:0000305"
FT CONFLICT 260
FT /note="V -> A (in Ref. 1; BAC27178)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 349 AA; 38845 MW; C89BAE59660DA5AF CRC64;
MARGRKMCKP RAVEAAAAAV AATAPGPEMV EQRGPGRPRS DGENVFAGQS KIYAYMSPNK
CSAMRSPLQE ENSVAHHEVK CPGKPLAGIY RKREEKRNTG NVIRSAVKSD EQKSKDTRRG
PLAPFPNQKS EAAEPPKTPP PSCDSTNVAV AKQALKKSLK GKQAPRKKSQ GKTQQNRKLT
DFYPVRRSSR KSKAELQSEE RKKNELIESG KEEGMKIDLI DGKGRGVIAT KQFSRGDFVV
EYHGDLIEIT DAKKREALYV QDPSTGCYMY YFQYLSKTYC VDATQETNRL GRLINHSKCG
NCQTKLHDID GVPHLILIAS RDIAAGEELL YDYGDRSKAS IEAYPWLKH
