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 24-JAN-2024, entry version 129. 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: 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.ENSMUSP00000098275; -. DR iPTMnet; Q2YDW7; -. DR PhosphoSitePlus; Q2YDW7; -. DR MaxQB; Q2YDW7; -. DR PaxDb; 10090-ENSMUSP00000052953; -. DR ProteomicsDB; 264787; -. DR GeneID; 67956; -. DR KEGG; mmu:67956; -. DR AGR; MGI:1915206; -. DR CTD; 387893; -. DR MGI; MGI:1915206; Kmt5a. DR eggNOG; KOG1085; Eukaryota. DR InParanoid; Q2YDW7; -. DR OrthoDB; 11811at2759; -. 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 82 CRISPR screens. DR ChiTaRS; Kmt5a; mouse. DR PRO; PR:Q2YDW7; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; Q2YDW7; Protein. DR GO; GO:0000785; C:chromatin; ISO:MGI. 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 H4K20 methyltransferase activity; ISO:MGI. DR GO; GO:0140944; F:histone H4K20 monomethyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0042054; F:histone methyltransferase activity; 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:0045892; P:negative regulation of DNA-templated transcription; ISO:MGI. DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; ISO:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB. 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 CDD; cd10528; SET_SETD8; 1. DR Gene3D; 2.170.270.10; SET domain; 1. DR InterPro; IPR016858; KMT5A-like. DR InterPro; IPR047266; KMT5A-like_SET. DR InterPro; IPR001214; SET_dom. DR InterPro; IPR046341; SET_dom_sf. DR PANTHER; PTHR46167; N-LYSINE METHYLTRANSFERASE KMT5A; 1. DR PANTHER; PTHR46167:SF1; N-LYSINE METHYLTRANSFERASE KMT5A; 1. DR Pfam; PF00856; SET; 1. DR PIRSF; PIRSF027717; Histone_H4-K20_mtfrase; 1. DR SMART; SM00317; SET; 1. DR SUPFAM; SSF82199; SET domain; 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; 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 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 //