ID KMT5A_HUMAN Reviewed; 393 AA. AC Q9NQR1; A8K9D0; Q86W83; Q8TD09; DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 15-NOV-2002, sequence version 3. DT 27-MAR-2024, entry version 204. DE RecName: Full=N-lysine methyltransferase KMT5A {ECO:0000305}; DE EC=2.1.1.- {ECO:0000305|PubMed:17707234}; DE AltName: Full=H4-K20-HMTase KMT5A; DE AltName: Full=Histone-lysine N-methyltransferase KMT5A; DE EC=2.1.1.361 {ECO:0000269|PubMed:12086618, ECO:0000269|PubMed:12121615, ECO:0000269|PubMed:15964846, ECO:0000269|PubMed:27338793}; DE AltName: Full=Lysine N-methyltransferase 5A; DE AltName: Full=Lysine-specific methylase 5A {ECO:0000312|HGNC:HGNC:29489}; DE AltName: Full=PR/SET domain-containing protein 07; DE Short=PR-Set7 {ECO:0000303|PubMed:23468428}; DE Short=PR/SET07; DE AltName: Full=SET domain-containing protein 8; GN Name=KMT5A {ECO:0000312|HGNC:HGNC:29489}; GN Synonyms=PRSET7, SET07, SET8, SETD8; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 108-131; RP 220-231 AND 349-393, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, RP AND MUTAGENESIS OF ARG-336. RC TISSUE=Cervix carcinoma; 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 [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 83-103; RP 109-134; 141-151; 162-172; 221-230; 245-260; 280-297 AND 350-393, FUNCTION, RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-340 AND 385-ILE--HIS-393. 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 [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Tain F., Huang S.; RT "A novel PR/SET domain-containing gene, SET07, as a candidate tumor RT suppressor."; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Thymus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; 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 [6] RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE. RX PubMed=12208845; DOI=10.1101/gad.1014902; RA Rice J.C., Nishioka K., Sarma K., Steward R., Reinberg D., Allis C.D.; RT "Mitotic-specific methylation of histone H4 Lys 20 follows increased PR- RT Set7 expression and its localization to mitotic chromosomes."; RL Genes Dev. 16:2225-2230(2002). RN [7] RP FUNCTION, AND INDUCTION. RX PubMed=15200950; DOI=10.1016/j.molcel.2004.06.008; RA Julien E., Herr W.; RT "A switch in mitotic histone H4 lysine 20 methylation status is linked to M RT phase defects upon loss of HCF-1."; RL Mol. Cell 14:713-725(2004). RN [8] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=15964846; DOI=10.1074/jbc.m501691200; RA Yin Y., Liu C., Tsai S.N., Zhou B., Ngai S.M., Zhu G.; RT "SET8 recognizes the sequence RHRK20VLRDN within the N terminus of histone RT H4 and mono-methylates lysine 20."; RL J. Biol. Chem. 280:30025-30031(2005). RN [9] RP FUNCTION. RX PubMed=16517599; DOI=10.1074/jbc.m513462200; RA Sims J.K., Houston S.I., Magazinnik T., Rice J.C.; RT "A trans-tail histone code defined by monomethylated H4 Lys-20 and H3 Lys-9 RT demarcates distinct regions of silent chromatin."; RL J. Biol. Chem. 281:12760-12766(2006). RN [10] RP FUNCTION, AND MUTAGENESIS OF ASP-379. RX PubMed=17707234; DOI=10.1016/j.molcel.2007.07.012; RA Shi X., Kachirskaia I., Yamaguchi H., West L.E., Wen H., Wang E.W., RA Dutta S., Appella E., Gozani O.; RT "Modulation of p53 function by SET8-mediated methylation at lysine 382."; RL Mol. Cell 27:636-646(2007). RN [11] RP INTERACTION WITH L3MBTL1. RX PubMed=18408754; DOI=10.1038/onc.2008.67; RA Kalakonda N., Fischle W., Boccuni P., Gurvich N., Hoya-Arias R., Zhao X., RA Miyata Y., Macgrogan D., Zhang J., Sims J.K., Rice J.C., Nimer S.D.; RT "Histone H4 lysine 20 monomethylation promotes transcriptional repression RT by L3MBTL1."; RL Oncogene 27:4293-4304(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-100, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP MUTAGENESIS OF ASP-379. RX PubMed=20870725; DOI=10.1074/jbc.m110.139527; RA West L.E., Roy S., Lachmi-Weiner K., Hayashi R., Shi X., Appella E., RA Kutateladze T.G., Gozani O.; RT "The MBT repeats of L3MBTL1 link SET8-mediated p53 methylation at lysine RT 382 to target gene repression."; RL J. Biol. Chem. 285:37725-37732(2010). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-100, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [15] RP ACETYLATION AT LYS-162, DEACETYLATION AT LYS-162 BY SIRT2, INTERACTION WITH RP SIRT2, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-162, AND MASS SPECTROMETRY RP (ISOFORM 2). 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). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-181, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [17] RP FUNCTION, INDUCTION, UBIQUITINATION, AND MUTAGENESIS OF ARG-336 AND RP ASP-379. RX PubMed=23478445; DOI=10.1016/j.molcel.2013.02.003; RA Abbas T., Mueller A.C., Shibata E., Keaton M., Rossi M., Dutta A.; RT "CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr- RT Set7/Set8-mediated cellular migration."; RL Mol. Cell 49:1147-1158(2013). RN [18] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=27338793; DOI=10.1038/nature18312; RA Saredi G., Huang H., Hammond C.M., Alabert C., Bekker-Jensen S., Forne I., RA Reveron-Gomez N., Foster B.M., Mlejnkova L., Bartke T., Cejka P., RA Mailand N., Imhof A., Patel D.J., Groth A.; RT "H4K20me0 marks post-replicative chromatin and recruits the TONSL-MMS22L RT DNA repair complex."; RL Nature 534:714-718(2016). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 233-393 IN COMPLEX WITH HISTONE H4 RP AND S-ADENOSYLMETHIONINE, AND FUNCTION. RX PubMed=15933069; DOI=10.1101/gad.1315905; RA Xiao B., Jing C., Kelly G., Walker P.A., Muskett F.W., Frenkiel T.A., RA Martin S.R., Sarma K., Reinberg D., Gamblin S.J., Wilson J.R.; RT "Specificity and mechanism of the histone methyltransferase Pr-Set7."; RL Genes Dev. 19:1444-1454(2005). RN [20] RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 231-393 IN COMPLEX WITH HISTONE RP H4 AND S-ADENOSYLMETHIONINE, FUNCTION, AND MUTAGENESIS OF TYR-286; GLU-300; RP CYS-311; TYR-375; ASP-379 AND HIS-388. RX PubMed=15933070; DOI=10.1101/gad.1318405; RA Couture J.-F., Collazo E., Brunzelle J.S., Trievel R.C.; RT "Structural and functional analysis of SET8, a histone H4 'Lys-20' RT methyltransferase."; RL Genes Dev. 19:1455-1465(2005). CC -!- FUNCTION: Protein-lysine N-methyltransferase that monomethylates both CC histones and non-histone proteins (PubMed:12086618, PubMed:12121615, CC PubMed:15964846, PubMed:17707234, PubMed:27338793). Specifically CC monomethylates 'Lys-20' of histone H4 (H4K20me1) (PubMed:12086618, CC PubMed:12121615, PubMed:15964846, PubMed:27338793, PubMed:15200950, CC PubMed:15933069, PubMed:15933070, PubMed:16517599). H4K20me1 is CC enriched during mitosis and represents a specific tag for epigenetic CC transcriptional repression (PubMed:12086618, PubMed:12121615, CC PubMed:15964846, PubMed:15200950, PubMed:15933069, PubMed:15933070, CC PubMed:16517599). Mainly functions in euchromatin regions, thereby CC playing a central role in the silencing of euchromatic genes CC (PubMed:12086618, PubMed:12121615, PubMed:15964846, PubMed:15200950, CC PubMed:15933069, PubMed:15933070, PubMed:16517599). Required for cell CC proliferation, probably by contributing to the maintenance of proper CC higher-order structure of DNA during mitosis (PubMed:12086618, CC PubMed:12121615, PubMed:15964846, PubMed:15200950, PubMed:15933069, CC PubMed:15933070, PubMed:16517599). Involved in chromosome condensation CC and proper cytokinesis (PubMed:12086618, PubMed:12121615, CC PubMed:15964846, PubMed:15200950, PubMed:15933069, PubMed:15933070, CC PubMed:16517599). Nucleosomes are preferred as substrate compared to CC free histones (PubMed:12086618, PubMed:12121615, PubMed:15964846, CC PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:16517599). CC Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress CC p53/TP53-target genes (PubMed:17707234). Plays a negative role in TGF- CC beta response regulation and a positive role in cell migration CC (PubMed:23478445). {ECO:0000269|PubMed:12086618, CC ECO:0000269|PubMed:12121615, ECO:0000269|PubMed:15200950, CC ECO:0000269|PubMed:15933069, ECO:0000269|PubMed:15933070, CC ECO:0000269|PubMed:15964846, ECO:0000269|PubMed:16517599, CC ECO:0000269|PubMed:17707234, ECO:0000269|PubMed:23478445, CC ECO:0000269|PubMed:27338793}. 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:12086618, ECO:0000269|PubMed:12121615, CC ECO:0000269|PubMed:15964846, ECO:0000269|PubMed:27338793}; 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:0000305|PubMed:17707234}; CC -!- SUBUNIT: Interacts with L3MBTL1. {ECO:0000269|PubMed:18408754}. CC -!- SUBUNIT: [Isoform 2]: Interacts with SIRT2 (phosphorylated form); the CC interaction is direct, stimulates KMT5A-mediated methyltransferase CC activity at histone H4 'Lys-20' (H4K20me1) and is increased in a CC H(2)O(2)-induced oxidative stress-dependent manner. CC {ECO:0000269|PubMed:23468428}. CC -!- INTERACTION: CC Q9NQR1; P62805: H4C9; NbExp=6; IntAct=EBI-1268946, EBI-302023; CC Q9NQR1; P07910: HNRNPC; NbExp=2; IntAct=EBI-1268946, EBI-357966; CC Q9NQR1; Q15672: TWIST1; NbExp=5; IntAct=EBI-1268946, EBI-1797287; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12086618}. Chromosome CC {ECO:0000269|PubMed:12086618, ECO:0000269|PubMed:12208845, CC ECO:0000269|PubMed:23468428}. Note=Specifically localizes to mitotic CC chromosomes (PubMed:12208845). Colocalized with SIRT2 at mitotic foci CC (PubMed:23468428). Associates with chromosomes during mitosis; CC association is increased in a H(2)O(2)-induced oxidative stress- CC dependent manner (PubMed:23468428). Associates with silent chromatin on CC euchromatic arms (PubMed:12086618). Not associated with constitutive CC heterochromatin (PubMed:12086618). {ECO:0000269|PubMed:12086618, CC ECO:0000269|PubMed:12208845, ECO:0000269|PubMed:23468428}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9NQR1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NQR1-2; Sequence=VSP_002226, VSP_002227; CC -!- DEVELOPMENTAL STAGE: Not detected during G1 phase. First detected CC during S through G2 phases, and peaks during mitosis (at protein CC level). {ECO:0000269|PubMed:12208845}. CC -!- INDUCTION: By HCFC1 C-terminal chain, independently of HCFC1 N-terminal CC chain. Transiently induced by TGF-beta and during the cell cycle. CC {ECO:0000269|PubMed:15200950, ECO:0000269|PubMed:23478445}. 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. {ECO:0000269|PubMed:12086618, CC ECO:0000269|PubMed:12121615}. CC -!- PTM: Acetylated at Lys-162; does not affect methyltransferase activity. CC Deacetylated at Lys-162 possibly by SIRT2; does not change CC methyltransferase activity. {ECO:0000269|PubMed:23468428}. CC -!- PTM: Ubiquitinated and degraded by the DCX(DTL) complex. CC {ECO:0000305|PubMed:23478445}. 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 -!- CAUTION: It is uncertain whether Met-1 or Met-72 is the initiator. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAL40879.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AY064546; AAL40879.1; ALT_INIT; mRNA. DR EMBL; AY102937; AAM47033.1; -; mRNA. DR EMBL; AF287261; AAF97812.2; -; mRNA. DR EMBL; AK292645; BAF85334.1; -; mRNA. DR EMBL; BC050346; AAH50346.1; -; mRNA. DR CCDS; CCDS9247.1; -. [Q9NQR1-2] DR RefSeq; NP_001311433.1; NM_001324504.1. DR RefSeq; NP_001311434.1; NM_001324505.1. DR RefSeq; NP_001311435.1; NM_001324506.1. DR RefSeq; NP_065115.3; NM_020382.4. [Q9NQR1-2] DR PDB; 1ZKK; X-ray; 1.45 A; A/B/C/D=231-393. DR PDB; 2BQZ; X-ray; 1.50 A; A/E=233-393. DR PDB; 3F9W; X-ray; 1.60 A; A/B/C/D=232-393. DR PDB; 3F9X; X-ray; 1.25 A; A/B/C/D=232-393. DR PDB; 3F9Y; X-ray; 1.50 A; A/B=232-393. DR PDB; 3F9Z; X-ray; 1.60 A; A/B/C/D=232-393. DR PDB; 4IJ8; X-ray; 2.00 A; A/B=232-393. DR PDB; 5HQ2; X-ray; 4.50 A; M=194-393. DR PDB; 5T5G; X-ray; 2.10 A; A=234-380. DR PDB; 5TEG; X-ray; 1.30 A; A/B=234-393. DR PDB; 5TH7; X-ray; 1.95 A; A/B=234-380. DR PDB; 5V2N; X-ray; 2.00 A; A=231-393. DR PDB; 5W1Y; X-ray; 1.70 A; A/B=232-393. DR PDB; 6BOZ; X-ray; 2.40 A; A/B=232-393. DR PDB; 7D1Z; EM; 3.15 A; K=45-393. DR PDB; 7D20; EM; 3.00 A; K=45-393. DR PDB; 7XPX; EM; 3.20 A; K=194-393. DR PDBsum; 1ZKK; -. DR PDBsum; 2BQZ; -. DR PDBsum; 3F9W; -. DR PDBsum; 3F9X; -. DR PDBsum; 3F9Y; -. DR PDBsum; 3F9Z; -. DR PDBsum; 4IJ8; -. DR PDBsum; 5HQ2; -. DR PDBsum; 5T5G; -. DR PDBsum; 5TEG; -. DR PDBsum; 5TH7; -. DR PDBsum; 5V2N; -. DR PDBsum; 5W1Y; -. DR PDBsum; 6BOZ; -. DR PDBsum; 7D1Z; -. DR PDBsum; 7D20; -. DR PDBsum; 7XPX; -. DR AlphaFoldDB; Q9NQR1; -. DR EMDB; EMD-30551; -. DR EMDB; EMD-30552; -. DR EMDB; EMD-33385; -. DR SMR; Q9NQR1; -. DR BioGRID; 132490; 76. DR DIP; DIP-39133N; -. DR IntAct; Q9NQR1; 39. DR MINT; Q9NQR1; -. DR STRING; 9606.ENSP00000384629; -. DR BindingDB; Q9NQR1; -. DR ChEMBL; CHEMBL1795176; -. DR GuidetoPHARMACOLOGY; 2704; -. DR GlyGen; Q9NQR1; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9NQR1; -. DR PhosphoSitePlus; Q9NQR1; -. DR BioMuta; KMT5A; -. DR DMDM; 25091219; -. DR EPD; Q9NQR1; -. DR jPOST; Q9NQR1; -. DR MassIVE; Q9NQR1; -. DR MaxQB; Q9NQR1; -. DR PaxDb; 9606-ENSP00000384629; -. DR PeptideAtlas; Q9NQR1; -. DR ProteomicsDB; 82171; -. [Q9NQR1-1] DR ProteomicsDB; 82172; -. [Q9NQR1-2] DR Pumba; Q9NQR1; -. DR Antibodypedia; 31806; 699 antibodies from 37 providers. DR DNASU; 387893; -. DR Ensembl; ENST00000402868.8; ENSP00000384629.3; ENSG00000183955.14. [Q9NQR1-2] DR GeneID; 387893; -. DR KEGG; hsa:387893; -. DR MANE-Select; ENST00000402868.8; ENSP00000384629.3; NM_020382.7; NP_065115.3. [Q9NQR1-2] DR UCSC; uc001uew.4; human. [Q9NQR1-1] DR AGR; HGNC:29489; -. DR CTD; 387893; -. DR DisGeNET; 387893; -. DR GeneCards; KMT5A; -. DR HGNC; HGNC:29489; KMT5A. DR HPA; ENSG00000183955; Low tissue specificity. DR MIM; 607240; gene. DR neXtProt; NX_Q9NQR1; -. DR OpenTargets; ENSG00000183955; -. DR PharmGKB; PA143485616; -. DR VEuPathDB; HostDB:ENSG00000183955; -. DR eggNOG; KOG1085; Eukaryota. DR GeneTree; ENSGT00940000160030; -. DR InParanoid; Q9NQR1; -. DR OMA; LSCDSPN; -. DR OrthoDB; 11811at2759; -. DR PhylomeDB; Q9NQR1; -. DR TreeFam; TF335181; -. DR BioCyc; MetaCyc:HS11381-MONOMER; -. DR BRENDA; 2.1.1.361; 2681. DR BRENDA; 2.1.1.362; 2681. DR PathwayCommons; Q9NQR1; -. DR Reactome; R-HSA-2299718; Condensation of Prophase Chromosomes. DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines. DR Reactome; R-HSA-6804760; Regulation of TP53 Activity through Methylation. DR SABIO-RK; Q9NQR1; -. DR SignaLink; Q9NQR1; -. DR SIGNOR; Q9NQR1; -. DR BioGRID-ORCS; 387893; 105 hits in 1140 CRISPR screens. DR ChiTaRS; KMT5A; human. DR EvolutionaryTrace; Q9NQR1; -. DR GeneWiki; SETD8; -. DR GenomeRNAi; 387893; -. DR Pharos; Q9NQR1; Tchem. DR PRO; PR:Q9NQR1; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q9NQR1; Protein. DR Bgee; ENSG00000183955; Expressed in sural nerve and 130 other cell types or tissues. DR ExpressionAtlas; Q9NQR1; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:UniProt. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005700; C:polytene chromosome; IBA:GO_Central. DR GO; GO:0140939; F:histone H4 methyltransferase activity; TAS:Reactome. DR GO; GO:0042799; F:histone H4K20 methyltransferase activity; IDA:UniProtKB. DR GO; GO:0140944; F:histone H4K20 monomethyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0042054; F:histone methyltransferase activity; IDA:UniProtKB. DR GO; GO:0016278; F:lysine N-methyltransferase activity; TAS:Reactome. DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; IDA:UniProtKB. DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0007076; P:mitotic chromosome condensation; TAS:Reactome. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; IDA:UniProt. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0018026; P:peptidyl-lysine monomethylation; IDA:UniProtKB. DR GO; GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB. DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome. 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 IDEAL; IID00101; -. 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 SMART; SM00317; SET; 1. DR SUPFAM; SSF82199; SET domain; 1. DR PROSITE; PS51571; SAM_MT43_PR_SET; 1. DR PROSITE; PS50280; SET; 1. DR Genevisible; Q9NQR1; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division; KW Chromatin regulator; Chromosome; Coiled coil; Direct protein sequencing; KW Methyltransferase; Mitosis; Nucleus; Phosphoprotein; Reference proteome; KW Repressor; S-adenosyl-L-methionine; Transcription; KW Transcription regulation; Transferase; Ubl conjugation. FT CHAIN 1..393 FT /note="N-lysine methyltransferase KMT5A" FT /id="PRO_0000186081" FT DOMAIN 257..378 FT /note="SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT REGION 68..88 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 135..241 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 134..163 FT /evidence="ECO:0000255" FT COMPBIAS 202..216 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 226..241 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 267..269 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT BINDING 312 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT BINDING 339..340 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT MOD_RES 100 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 162 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:23468428" FT MOD_RES 181 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..41 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12121615, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334" FT /id="VSP_002226" FT VAR_SEQ 42..57 FT /note="PGRAAGGKMSKPCAVE -> MARGRKMSKPRAVEAA (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12121615, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334" FT /id="VSP_002227" FT MUTAGEN 162 FT /note="K->Q: Does not affect the interaction with SIRT2. FT Increases the number of mitotic foci formation. Does not FT affect methyltransferase activity." FT /evidence="ECO:0000269|PubMed:23468428" FT MUTAGEN 162 FT /note="K->R: Increases the interaction with SIRT2. Reduces FT the number of mitotic foci formation. Does not affect FT methyltransferase activity." FT /evidence="ECO:0000269|PubMed:23468428" FT MUTAGEN 286 FT /note="Y->A,F: Strongly reduces affinity for histone H4 and FT abolishes methyltransferase activity." FT /evidence="ECO:0000269|PubMed:15933070" FT MUTAGEN 300 FT /note="E->A: Strongly reduces affinity for histone H4." FT /evidence="ECO:0000269|PubMed:15933070" FT MUTAGEN 311 FT /note="C->A: Strongly reduces affinity for histone H4." FT /evidence="ECO:0000269|PubMed:15933070" FT MUTAGEN 336 FT /note="R->G: Abolishes methyltransferase activity." FT /evidence="ECO:0000269|PubMed:12086618, FT ECO:0000269|PubMed:23478445" FT MUTAGEN 340 FT /note="H->A: Strongly decreases methyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:12121615" FT MUTAGEN 375 FT /note="Y->A: Strongly reduces affinity for histone H4 and FT methyltransferase activity." FT /evidence="ECO:0000269|PubMed:15933070" FT MUTAGEN 375 FT /note="Y->F: Alters methyltransferase activity, so that FT both monomethylation and dimethylation take place." FT /evidence="ECO:0000269|PubMed:15933070" FT MUTAGEN 379 FT /note="D->A,N: Abolishes histone H4 binding and FT methyltransferase activity." FT /evidence="ECO:0000269|PubMed:15933070, FT ECO:0000269|PubMed:17707234, ECO:0000269|PubMed:20870725, FT ECO:0000269|PubMed:23478445" FT MUTAGEN 385..393 FT /note="Missing: Abolishes methyltransferase activity." FT /evidence="ECO:0000269|PubMed:12121615" FT MUTAGEN 388 FT /note="H->A,E: Strongly reduces affinity for histone H4." FT /evidence="ECO:0000269|PubMed:15933070" FT MUTAGEN 388 FT /note="H->F: Increases affinity for histone H4." FT /evidence="ECO:0000269|PubMed:15933070" FT CONFLICT 162..163 FT /note="KG -> RR (in Ref. 3; AAF97812)" FT /evidence="ECO:0000305" FT CONFLICT 281 FT /note="D -> A (in Ref. 3; AAF97812)" FT /evidence="ECO:0000305" FT CONFLICT 343 FT /note="C -> R (in Ref. 3; AAF97812)" FT /evidence="ECO:0000305" FT CONFLICT 357 FT /note="P -> R (in Ref. 5; AAH50346)" FT /evidence="ECO:0000305" FT CONFLICT 373 FT /note="L -> P (in Ref. 3; AAF97812)" FT /evidence="ECO:0000305" FT HELIX 236..253 FT /evidence="ECO:0007829|PDB:3F9X" FT STRAND 259..264 FT /evidence="ECO:0007829|PDB:3F9X" FT TURN 265..267 FT /evidence="ECO:0007829|PDB:3F9X" FT STRAND 268..275 FT /evidence="ECO:0007829|PDB:3F9X" FT STRAND 282..285 FT /evidence="ECO:0007829|PDB:3F9X" FT STRAND 288..292 FT /evidence="ECO:0007829|PDB:3F9X" FT HELIX 293..303 FT /evidence="ECO:0007829|PDB:3F9X" FT HELIX 307..309 FT /evidence="ECO:0007829|PDB:5TH7" FT HELIX 310..312 FT /evidence="ECO:0007829|PDB:4IJ8" FT STRAND 313..318 FT /evidence="ECO:0007829|PDB:3F9X" FT STRAND 321..326 FT /evidence="ECO:0007829|PDB:3F9X" FT HELIX 335..337 FT /evidence="ECO:0007829|PDB:3F9X" FT STRAND 338..340 FT /evidence="ECO:0007829|PDB:5TH7" FT STRAND 345..353 FT /evidence="ECO:0007829|PDB:3F9X" FT STRAND 356..365 FT /evidence="ECO:0007829|PDB:3F9X" FT STRAND 372..375 FT /evidence="ECO:0007829|PDB:5TH7" FT TURN 377..380 FT /evidence="ECO:0007829|PDB:5V2N" FT HELIX 382..387 FT /evidence="ECO:0007829|PDB:3F9X" FT HELIX 389..392 FT /evidence="ECO:0007829|PDB:3F9X" SQ SEQUENCE 393 AA; 42890 MW; 2DCD9B697834B5BD CRC64; MGEGGAAAAL VAAAAAAAAA AAAVVAGQRR RRLGRRARCH GPGRAAGGKM SKPCAVEAAA AAVAATAPGP EMVERRGPGR PRTDGENVFT GQSKIYSYMS PNKCSGMRFP LQEENSVTHH EVKCQGKPLA GIYRKREEKR NAGNAVRSAM KSEEQKIKDA RKGPLVPFPN QKSEAAEPPK TPPSSCDSTN AAIAKQALKK PIKGKQAPRK KAQGKTQQNR KLTDFYPVRR SSRKSKAELQ SEERKRIDEL IESGKEEGMK IDLIDGKGRG VIATKQFSRG DFVVEYHGDL IEITDAKKRE ALYAQDPSTG CYMYYFQYLS KTYCVDATRE TNRLGRLINH SKCGNCQTKL HDIDGVPHLI LIASRDIAAG EELLYDYGDR SKASIEAHPW LKH //