GenomeNet

Database: UniProt/SWISS-PROT
Entry: KMT5A_HUMAN
LinkDB: KMT5A_HUMAN
Original site: 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   05-DEC-2018, entry version 172.
DE   RecName: Full=N-lysine methyltransferase KMT5A {ECO:0000305};
DE            EC=2.1.1.-;
DE   AltName: Full=H4-K20-HMTase KMT5A;
DE   AltName: Full=Histone-lysine N-methyltransferase KMT5A;
DE            EC=2.1.1.43;
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RP   ACTIVITY, 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.,
RA   Wang Y., Chuikov S., Valenzuela P., Tempst P., Steward R., Lis J.T.,
RA   Allis C.D., Reinberg D.;
RT   "PR-Set7 is a nucleosome-specific methyltransferase that modifies
RT   lysine 20 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,
RP   FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-340 AND
RP   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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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
RT   project: 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
RT   PR-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
RT   to M phase defects upon loss of HCF-1.";
RL   Mol. Cell 14:713-725(2004).
RN   [8]
RP   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
RT   histone 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
RT   Lys-9 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
RT   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.,
RA   Zhao X., Miyata Y., Macgrogan D., Zhang J., Sims J.K., Rice J.C.,
RA   Nimer S.D.;
RT   "Histone H4 lysine 20 monomethylation promotes transcriptional
RT   repression by L3MBTL1.";
RL   Oncogene 27:4293-4304(2008).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-100, AND IDENTIFICATION
RP   BY 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
RT   lysine 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
RP   BY 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.,
RA   Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full
RT   phosphorylation 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
RP   WITH SIRT2, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-172, AND MASS
RP   SPECTROMETRY (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.,
RA   Rabanal R.M., Fondevila D., Munoz P., Kruger M., Tischfield J.A.,
RA   Vaquero A.;
RT   "The tumor suppressor SirT2 regulates cell cycle progression and
RT   genome stability by modulating the mitotic deposition of H4K20
RT   methylation.";
RL   Genes Dev. 27:639-653(2013).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-181, AND IDENTIFICATION
RP   BY 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
RT   regulates Pr-Set7/Set8-mediated cellular migration.";
RL   Mol. Cell 49:1147-1158(2013).
RN   [18]
RP   X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 233-393 IN COMPLEX WITH
RP   HISTONE H4 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   [19]
RP   X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 231-393 IN COMPLEX WITH
RP   HISTONE H4 AND S-ADENOSYLMETHIONINE, FUNCTION, AND MUTAGENESIS OF
RP   TYR-286; GLU-300; 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
CC       both histones and non-histone proteins. Specifically
CC       monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is
CC       enriched during mitosis and represents a specific tag for
CC       epigenetic transcriptional repression. Mainly functions in
CC       euchromatin regions, thereby playing a central role in the
CC       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
CC       condensation and proper cytokinesis. Nucleosomes are preferred as
CC       substrate compared to free histones. Mediates monomethylation of
CC       p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes.
CC       Plays a negative role in TGF-beta response regulation and a
CC       positive role in cell migration. {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:16517599, ECO:0000269|PubMed:17707234,
CC       ECO:0000269|PubMed:23478445}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[histone] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl-[histone] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:10024, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:9846,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.43;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU00904,
CC         ECO:0000269|PubMed:12086618, ECO:0000269|PubMed:12121615,
CC         ECO:0000269|PubMed:15964846};
CC   -!- SUBUNIT: Interacts with L3MBTL1. Isoform 2 interacts with SIRT2
CC       (phosphorylated form); the interaction is direct, stimulates
CC       KMT5A-mediated methyltransferase activity at histone H4 'Lys-20'
CC       (H4K20me1) and is increased in a H(2)O(2)-induced oxidative
CC       stress-dependent manner. {ECO:0000269|PubMed:15933069,
CC       ECO:0000269|PubMed:15933070, ECO:0000269|PubMed:18408754,
CC       ECO:0000269|PubMed:23468428}.
CC   -!- INTERACTION:
CC       P62805:HIST2H4B; NbExp=5; IntAct=EBI-1268946, EBI-302023;
CC       Q15672:TWIST1; NbExp=5; IntAct=EBI-1268946, EBI-1797287;
CC   -!- SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Specifically
CC       localizes to mitotic chromosomes. Colocalized with SIRT2 at
CC       mitotic foci. Associates with chromosomes during mitosis;
CC       association is increased in a H(2)O(2)-induced oxidative stress-
CC       dependent manner. Associates with silent chromatin on euchromatic
CC       arms. Not associated with constitutive heterochromatin.
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-
CC       terminal chain. Transiently induced by TGF-beta and during the
CC       cell cycle. {ECO:0000269|PubMed:15200950,
CC       ECO:0000269|PubMed:23478445}.
CC   -!- DOMAIN: Although the SET domain contains the active site of
CC       enzymatic activity, both sequences upstream and downstream of the
CC       SET domain are required for methyltransferase activity.
CC   -!- PTM: Acetylated at Lys-172; does not change methyltransferase
CC       activity. Deacetylated at Lys-172 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
CC       methyltransferase superfamily. Histone-lysine methyltransferase
CC       family. PR/SET subfamily. {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=Translation N-terminally extended.; Evidence={ECO:0000305};
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   UniGene; Hs.443735; -.
DR   UniGene; Hs.572262; -.
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   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   ProteinModelPortal; Q9NQR1; -.
DR   SMR; Q9NQR1; -.
DR   BioGrid; 132490; 29.
DR   DIP; DIP-39133N; -.
DR   IntAct; Q9NQR1; 3.
DR   MINT; Q9NQR1; -.
DR   STRING; 9606.ENSP00000332995; -.
DR   BindingDB; Q9NQR1; -.
DR   ChEMBL; CHEMBL1795176; -.
DR   GuidetoPHARMACOLOGY; 2704; -.
DR   iPTMnet; Q9NQR1; -.
DR   PhosphoSitePlus; Q9NQR1; -.
DR   DMDM; 25091219; -.
DR   MaxQB; Q9NQR1; -.
DR   PaxDb; Q9NQR1; -.
DR   PeptideAtlas; Q9NQR1; -.
DR   PRIDE; Q9NQR1; -.
DR   ProteomicsDB; 82171; -.
DR   ProteomicsDB; 82172; -. [Q9NQR1-2]
DR   DNASU; 387893; -.
DR   Ensembl; ENST00000402868; ENSP00000384629; ENSG00000183955. [Q9NQR1-2]
DR   GeneID; 387893; -.
DR   KEGG; hsa:387893; -.
DR   UCSC; uc001uew.4; human. [Q9NQR1-1]
DR   CTD; 387893; -.
DR   DisGeNET; 387893; -.
DR   EuPathDB; HostDB:ENSG00000183955.12; -.
DR   GeneCards; KMT5A; -.
DR   H-InvDB; HIX0037637; -.
DR   HGNC; HGNC:29489; KMT5A.
DR   HPA; HPA064495; -.
DR   MIM; 607240; gene.
DR   neXtProt; NX_Q9NQR1; -.
DR   OpenTargets; ENSG00000183955; -.
DR   PharmGKB; PA143485616; -.
DR   eggNOG; KOG1085; Eukaryota.
DR   eggNOG; COG2940; LUCA.
DR   GeneTree; ENSGT00940000160030; -.
DR   HOGENOM; HOG000020818; -.
DR   HOVERGEN; HBG067546; -.
DR   InParanoid; Q9NQR1; -.
DR   KO; K11428; -.
DR   OMA; KWCIDAT; -.
DR   OrthoDB; EOG091G0UBI; -.
DR   PhylomeDB; Q9NQR1; -.
DR   TreeFam; TF335181; -.
DR   BRENDA; 2.1.1.43; 2681.
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   SIGNOR; Q9NQR1; -.
DR   EvolutionaryTrace; Q9NQR1; -.
DR   GeneWiki; SETD8; -.
DR   GenomeRNAi; 387893; -.
DR   PRO; PR:Q9NQR1; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   Bgee; ENSG00000183955; Expressed in 148 organ(s), highest expression level in esophagus mucosa.
DR   CleanEx; HS_SETD8; -.
DR   ExpressionAtlas; Q9NQR1; baseline and differential.
DR   Genevisible; Q9NQR1; HS.
DR   GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IDA:HPA.
DR   GO; GO:0042799; F:histone methyltransferase activity (H4-K20 specific); TAS:Reactome.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
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   InterPro; IPR016858; Hist_H4-K20_MeTrfase.
DR   InterPro; IPR001214; SET_dom.
DR   Pfam; PF00856; SET; 1.
DR   PIRSF; PIRSF027717; Histone_H4-K20_mtfrase; 1.
DR   SMART; SM00317; SET; 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;
KW   Cell division; Chromatin regulator; Chromosome; Coiled coil;
KW   Complete proteome; Direct protein sequencing; Methyltransferase;
KW   Mitosis; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW   S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW   Transferase; Ubl conjugation.
FT   CHAIN         1    393       N-lysine methyltransferase KMT5A.
FT                                /FTId=PRO_0000186081.
FT   DOMAIN      257    378       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   REGION      267    269       S-adenosyl-L-methionine binding.
FT   REGION      339    340       S-adenosyl-L-methionine binding.
FT   COILED      134    163       {ECO:0000255}.
FT   COMPBIAS      6     67       Ala-rich.
FT   COMPBIAS     29     32       Poly-Arg.
FT   BINDING     312    312       S-adenosyl-L-methionine.
FT   MOD_RES     100    100       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:20068231}.
FT   MOD_RES     172    172       N6-acetyllysine.
FT                                {ECO:0000269|PubMed:23468428}.
FT   MOD_RES     181    181       Phosphothreonine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   VAR_SEQ       1     41       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:12121615,
FT                                ECO:0000303|PubMed:14702039,
FT                                ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_002226.
FT   VAR_SEQ      42     57       PGRAAGGKMSKPCAVE -> MARGRKMSKPRAVEAA (in
FT                                isoform 2). {ECO:0000303|PubMed:12121615,
FT                                ECO:0000303|PubMed:14702039,
FT                                ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_002227.
FT   MUTAGEN     172    172       K->Q: Inhibits the interaction with
FT                                SIRT2. Increases the number of mitotic
FT                                foci formation. Does not change
FT                                methyltransferase activity.
FT                                {ECO:0000269|PubMed:23468428}.
FT   MUTAGEN     172    172       K->R: Increases the interaction with
FT                                SIRT2. Reduces the number of mitotic foci
FT                                formation. Does not change
FT                                methyltransferase activity.
FT                                {ECO:0000269|PubMed:23468428}.
FT   MUTAGEN     286    286       Y->A,F: Strongly reduces affinity for
FT                                histone H4 and abolishes
FT                                methyltransferase activity.
FT                                {ECO:0000269|PubMed:15933070}.
FT   MUTAGEN     300    300       E->A: Strongly reduces affinity for
FT                                histone H4.
FT                                {ECO:0000269|PubMed:15933070}.
FT   MUTAGEN     311    311       C->A: Strongly reduces affinity for
FT                                histone H4.
FT                                {ECO:0000269|PubMed:15933070}.
FT   MUTAGEN     336    336       R->G: Abolishes methyltransferase
FT                                activity. {ECO:0000269|PubMed:12086618,
FT                                ECO:0000269|PubMed:23478445}.
FT   MUTAGEN     340    340       H->A: Strongly decreases
FT                                methyltransferase activity.
FT                                {ECO:0000269|PubMed:12121615}.
FT   MUTAGEN     375    375       Y->A: Strongly reduces affinity for
FT                                histone H4 and methyltransferase
FT                                activity. {ECO:0000269|PubMed:15933070}.
FT   MUTAGEN     375    375       Y->F: Alters methyltransferase activity,
FT                                so that both monomethylation and
FT                                dimethylation take place.
FT                                {ECO:0000269|PubMed:15933070}.
FT   MUTAGEN     379    379       D->A,N: Abolishes histone H4 binding and
FT                                methyltransferase activity.
FT                                {ECO:0000269|PubMed:15933070,
FT                                ECO:0000269|PubMed:17707234,
FT                                ECO:0000269|PubMed:20870725,
FT                                ECO:0000269|PubMed:23478445}.
FT   MUTAGEN     385    393       Missing: Abolishes methyltransferase
FT                                activity. {ECO:0000269|PubMed:12121615}.
FT   MUTAGEN     388    388       H->A,E: Strongly reduces affinity for
FT                                histone H4.
FT                                {ECO:0000269|PubMed:15933070}.
FT   MUTAGEN     388    388       H->F: Increases affinity for histone H4.
FT                                {ECO:0000269|PubMed:15933070}.
FT   CONFLICT    162    163       KG -> RR (in Ref. 3; AAF97812).
FT                                {ECO:0000305}.
FT   CONFLICT    281    281       D -> A (in Ref. 3; AAF97812).
FT                                {ECO:0000305}.
FT   CONFLICT    343    343       C -> R (in Ref. 3; AAF97812).
FT                                {ECO:0000305}.
FT   CONFLICT    357    357       P -> R (in Ref. 5; AAH50346).
FT                                {ECO:0000305}.
FT   CONFLICT    373    373       L -> P (in Ref. 3; AAF97812).
FT                                {ECO:0000305}.
FT   HELIX       236    253       {ECO:0000244|PDB:3F9X}.
FT   STRAND      259    264       {ECO:0000244|PDB:3F9X}.
FT   TURN        265    267       {ECO:0000244|PDB:3F9X}.
FT   STRAND      268    275       {ECO:0000244|PDB:3F9X}.
FT   STRAND      282    285       {ECO:0000244|PDB:3F9X}.
FT   STRAND      288    292       {ECO:0000244|PDB:3F9X}.
FT   HELIX       293    303       {ECO:0000244|PDB:3F9X}.
FT   HELIX       307    309       {ECO:0000244|PDB:5TH7}.
FT   HELIX       310    312       {ECO:0000244|PDB:4IJ8}.
FT   STRAND      313    318       {ECO:0000244|PDB:3F9X}.
FT   STRAND      321    326       {ECO:0000244|PDB:3F9X}.
FT   HELIX       335    337       {ECO:0000244|PDB:3F9X}.
FT   STRAND      338    340       {ECO:0000244|PDB:5TH7}.
FT   STRAND      345    353       {ECO:0000244|PDB:3F9X}.
FT   STRAND      356    365       {ECO:0000244|PDB:3F9X}.
FT   STRAND      372    375       {ECO:0000244|PDB:5TH7}.
FT   TURN        377    380       {ECO:0000244|PDB:5V2N}.
FT   HELIX       382    387       {ECO:0000244|PDB:3F9X}.
FT   HELIX       389    392       {ECO:0000244|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
//
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