KMT5A_HUMAN
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 03-AUG-2022, entry version 195.
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;
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-172, DEACETYLATION AT LYS-172 BY SIRT2, INTERACTION WITH
RP SIRT2, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-172, 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-172; does not change methyltransferase activity.
CC Deacetylated at Lys-172 by SIRT2; does not change methyltransferase
CC 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};
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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 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 AlphaFoldDB; Q9NQR1; -.
DR SMR; Q9NQR1; -.
DR BioGRID; 132490; 71.
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 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; Q9NQR1; -.
DR PeptideAtlas; Q9NQR1; -.
DR PRIDE; Q9NQR1; -.
DR ProteomicsDB; 82171; -. [Q9NQR1-1]
DR ProteomicsDB; 82172; -. [Q9NQR1-2]
DR Antibodypedia; 31806; 615 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 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; THHEAKC; -.
DR OrthoDB; 1460495at2759; -.
DR PhylomeDB; Q9NQR1; -.
DR TreeFam; TF335181; -.
DR BioCyc; MetaCyc:HS11381-MON; -.
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; 90 hits in 1071 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 128 other tissues.
DR ExpressionAtlas; Q9NQR1; baseline and differential.
DR Genevisible; Q9NQR1; HS.
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:0042799; F:histone methyltransferase activity (H4-K20 specific); IDA:UniProtKB.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0016278; F:lysine N-methyltransferase activity; TAS:Reactome.
DR GO; GO:0002039; F:p53 binding; IPI:UniProtKB.
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:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0034771; P:histone H4-K20 monomethylation; IBA:GO_Central.
DR GO; GO:0007076; P:mitotic chromosome condensation; TAS:Reactome.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA: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 Gene3D; 2.170.270.10; -; 1.
DR IDEAL; IID00101; -.
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 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 172
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 172
FT /note="K->Q: Inhibits the interaction with SIRT2. Increases
FT the number of mitotic foci formation. Does not change
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:23468428"
FT MUTAGEN 172
FT /note="K->R: Increases the interaction with SIRT2. Reduces
FT the number of mitotic foci formation. Does not change
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
