KMT5B_HUMAN
ID KMT5B_HUMAN Reviewed; 885 AA.
AC Q4FZB7; A0A0A0MT19; B7WNX7; Q3SX56; Q4V775; Q6P150; Q96E44; Q9BUL0; Q9H022;
AC Q9H2K3; Q9NXV3; Q9Y393;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 5.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Histone-lysine N-methyltransferase KMT5B {ECO:0000305};
DE AltName: Full=Lysine N-methyltransferase 5B;
DE AltName: Full=Lysine-specific methyltransferase 5B {ECO:0000312|HGNC:HGNC:24283};
DE AltName: Full=Suppressor of variegation 4-20 homolog 1;
DE Short=Su(var)4-20 homolog 1;
DE Short=Suv4-20h1;
DE AltName: Full=[histone H4]-N-methyl-L-lysine20 N-methyltransferase KMT5B {ECO:0000305};
DE EC=2.1.1.362 {ECO:0000269|PubMed:24396869, ECO:0000269|PubMed:28114273};
DE AltName: Full=[histone H4]-lysine20 N-methyltransferase KMT5B {ECO:0000305};
DE EC=2.1.1.361 {ECO:0000269|PubMed:24396869};
GN Name=KMT5B {ECO:0000312|HGNC:HGNC:24283}; Synonyms=SUV420H1;
GN ORFNames=CGI-85;
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 [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-9.
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Mammary gland, Placenta, Testis, and Uterus;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 1-275 (ISOFORM 1).
RX PubMed=11401438; DOI=10.1006/geno.2000.6492;
RA Twells R.C.J., Metzker M.L., Brown S.D., Cox R., Garey C., Hammond H.,
RA Hey P.J., Levy E., Nakagawa Y., Philips M.S., Todd J.A., Hess J.F.;
RT "The sequence and gene characterization of a 400-kb candidate region for
RT IDDM4 on chromosome 11q13.";
RL Genomics 72:231-242(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-885 (ISOFORM 2).
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 442-884.
RC TISSUE=Colon;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 592-885.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP INDUCTION.
RX PubMed=16322686; DOI=10.4161/cbt.5.1.2288;
RA Tryndyak V.P., Kovalchuk O., Pogribny I.P.;
RT "Loss of DNA methylation and histone H4 lysine 20 trimethylation in human
RT breast cancer cells is associated with aberrant expression of DNA
RT methyltransferase 1, Suv4-20h2 histone methyltransferase and methyl-binding
RT proteins.";
RL Cancer Biol. Ther. 5:65-70(2006).
RN [8]
RP FUNCTION, INTERACTION WITH FRG1, AND SUBCELLULAR LOCATION.
RX PubMed=23720823; DOI=10.1093/jmcb/mjt018;
RA Neguembor M.V., Xynos A., Onorati M.C., Caccia R., Bortolanza S., Godio C.,
RA Pistoni M., Corona D.F., Schotta G., Gabellini D.;
RT "FSHD muscular dystrophy region gene 1 binds Suv4-20h1 histone
RT methyltransferase and impairs myogenesis.";
RL J. Mol. Cell Biol. 5:294-307(2013).
RN [9]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-555, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [10]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-555, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [11]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-555, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [12] {ECO:0007744|PDB:3S8P}
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 63-335 IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE AND ZINC, CATALYTIC ACTIVITY, FUNCTION,
RP BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLY-229; SER-251; TRP-264;
RP PHE-281 AND PHE-311, AND SUBUNIT.
RX PubMed=24396869; DOI=10.1016/j.febslet.2013.10.020;
RA Wu H., Siarheyeva A., Zeng H., Lam R., Dong A., Wu X.H., Li Y.,
RA Schapira M., Vedadi M., Min J.;
RT "Crystal structures of the human histone H4K20 methyltransferases SUV420H1
RT and SUV420H2.";
RL FEBS Lett. 587:3859-3868(2013).
RN [13] {ECO:0007744|PDB:5CPR}
RP X-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS) OF 69-335 IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE INHIBITOR AND ZINC, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, AND FUNCTION.
RX PubMed=28114273; DOI=10.1038/nchembio.2282;
RA Bromberg K.D., Mitchell T.R., Upadhyay A.K., Jakob C.G., Jhala M.A.,
RA Comess K.M., Lasko L.M., Li C., Tuzon C.T., Dai Y., Li F., Eram M.S.,
RA Nuber A., Soni N.B., Manaves V., Algire M.A., Sweis R.F., Torrent M.,
RA Schotta G., Sun C., Michaelides M.R., Shoemaker A.R., Arrowsmith C.H.,
RA Brown P.J., Santhakumar V., Martin A., Rice J.C., Chiang G.G., Vedadi M.,
RA Barsyte-Lovejoy D., Pappano W.N.;
RT "The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic
RT integrity.";
RL Nat. Chem. Biol. 13:317-324(2017).
RN [14] {ECO:0007744|PDB:5WBV}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 63-335 IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE INHIBITOR AND ZINC, AND SUBUNIT.
RA Halabelian L., Tempel W., Brown P.J., Bountra C., Edwards A.M.,
RA Arrowsmith C.H.;
RT "Crystal Structure of the SET Domain of Human SUV420H1 In Complex With
RT Inhibitor.";
RL Submitted (JUN-2017) to the PDB data bank.
RN [15]
RP INVOLVEMENT IN MRD51, AND VARIANTS MRD51 SER-264; VAL-513 AND GLN-540.
RX PubMed=28191889; DOI=10.1038/ng.3792;
RA Stessman H.A., Xiong B., Coe B.P., Wang T., Hoekzema K., Fenckova M.,
RA Kvarnung M., Gerdts J., Trinh S., Cosemans N., Vives L., Lin J.,
RA Turner T.N., Santen G., Ruivenkamp C., Kriek M., van Haeringen A., Aten E.,
RA Friend K., Liebelt J., Barnett C., Haan E., Shaw M., Gecz J.,
RA Anderlid B.M., Nordgren A., Lindstrand A., Schwartz C., Kooy R.F.,
RA Vandeweyer G., Helsmoortel C., Romano C., Alberti A., Vinci M., Avola E.,
RA Giusto S., Courchesne E., Pramparo T., Pierce K., Nalabolu S., Amaral D.G.,
RA Scheffer I.E., Delatycki M.B., Lockhart P.J., Hormozdiari F., Harich B.,
RA Castells-Nobau A., Xia K., Peeters H., Nordenskjoeld M., Schenck A.,
RA Bernier R.A., Eichler E.E.;
RT "Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes
RT with autism and developmental-disability biases.";
RL Nat. Genet. 49:515-526(2017).
RN [16]
RP VARIANT MRD51 187-ARG--ALA-885 DEL.
RX PubMed=29276005; DOI=10.1016/j.ajhg.2017.11.013;
RG Clinical Assessment of the Utility of Sequencing and Evaluation as a Service (CAUSES) Study;
RG Deciphering Developmental Disorders (DDD) Study;
RA Faundes V., Newman W.G., Bernardini L., Canham N., Clayton-Smith J.,
RA Dallapiccola B., Davies S.J., Demos M.K., Goldman A., Gill H., Horton R.,
RA Kerr B., Kumar D., Lehman A., McKee S., Morton J., Parker M.J., Rankin J.,
RA Robertson L., Temple I.K., Banka S.;
RT "Histone lysine methylases and demethylases in the landscape of human
RT developmental disorders.";
RL Am. J. Hum. Genet. 102:175-187(2018).
CC -!- FUNCTION: Histone methyltransferase that specifically methylates
CC monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2)
CC of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2)
CC and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription
CC and maintenance of genome integrity (PubMed:24396869, PubMed:28114273).
CC In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4
CC and nucleosomes (PubMed:24396869). H4 'Lys-20' trimethylation
CC represents a specific tag for epigenetic transcriptional repression.
CC Mainly functions in pericentric heterochromatin regions, thereby
CC playing a central role in the establishment of constitutive
CC heterochromatin in these regions. KMT5B is targeted to histone H3 via
CC its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By
CC similarity). Plays a role in myogenesis by regulating the expression of
CC target genes, such as EID3 (PubMed:23720823). Facilitates TP53BP1 foci
CC formation upon DNA damage and proficient non-homologous end-joining
CC (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of
CC 'Lys-20' of histone H4 (PubMed:28114273). May play a role in class
CC switch reconbination by catalyzing the di- and trimethylation of 'Lys-
CC 20' of histone H4 (By similarity). {ECO:0000250|UniProtKB:Q3U8K7,
CC ECO:0000269|PubMed:23720823, ECO:0000269|PubMed:24396869,
CC ECO:0000269|PubMed:28114273}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine
CC = H(+) + N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60348, Rhea:RHEA-COMP:15555, Rhea:RHEA-
CC COMP:15556, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976; EC=2.1.1.362;
CC Evidence={ECO:0000269|PubMed:24396869, ECO:0000269|PubMed:28114273};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60349;
CC Evidence={ECO:0000269|PubMed:28114273};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-
CC methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(20)-[histone H4]
CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:61992, Rhea:RHEA-
CC COMP:15556, Rhea:RHEA-COMP:15998, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961,
CC ChEBI:CHEBI:61976; Evidence={ECO:0000269|PubMed:28114273};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61993;
CC Evidence={ECO:0000269|PubMed:28114273};
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:0000269|PubMed:24396869};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60345;
CC Evidence={ECO:0000269|PubMed:24396869};
CC -!- ACTIVITY REGULATION: Inhibited by 6,7-Dichloro-N-cyclopentyl-4-
CC (pyridin-4-yl)phthalazin-1-amine (A-196) with an IC(50) of 25 nM. A-196
CC is competitive with the histone peptide substrate H4K20me1 but non
CC competitive with S-adenosyl-L-methionine.
CC {ECO:0000269|PubMed:28114273}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.4 uM for H4K20me0 {ECO:0000269|PubMed:24396869};
CC KM=1.7 uM for H4K20me1 {ECO:0000269|PubMed:24396869};
CC KM=0.3 uM for nucleosome {ECO:0000269|PubMed:24396869};
CC pH dependence:
CC Optimum pH is 8. {ECO:0000269|Ref.14};
CC -!- SUBUNIT: Homodimer (PubMed:24396869, Ref.14). Interacts with HP1
CC proteins CBX1, CBX3 and CBX5. Interacts with RB1 family proteins RB1,
CC RBL1 and RBL2 (By similarity). Interacts (via C-terminus) with FRG1.
CC {ECO:0000250, ECO:0000269|PubMed:23720823, ECO:0000269|PubMed:24396869,
CC ECO:0000269|Ref.14}.
CC -!- INTERACTION:
CC Q4FZB7; Q9H2G4: TSPYL2; NbExp=3; IntAct=EBI-1047962, EBI-947459;
CC Q4FZB7-1; Q61026: Ncoa2; Xeno; NbExp=4; IntAct=EBI-15746366, EBI-688662;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23720823}. Chromosome
CC {ECO:0000250}. Note=Associated with pericentric heterochromatin. CBX1
CC and CBX5 are required for the localization to pericentric
CC heterochromatin (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q4FZB7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q4FZB7-2; Sequence=VSP_024051, VSP_024052;
CC Name=3;
CC IsoId=Q4FZB7-4; Sequence=VSP_040034, VSP_040035;
CC -!- INDUCTION: Strongly down-regulated in breast cancer cells.
CC {ECO:0000269|PubMed:16322686}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 51
CC (MRD51) [MIM:617788]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period.
CC {ECO:0000269|PubMed:28191889, ECO:0000269|PubMed:29276005}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family. Suvar4-20
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00903}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD34080.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAG36937.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAH98121.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
CC Sequence=AAI04484.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA90905.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AP002992; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KC877427; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KC877429; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002522; AAH02522.2; -; mRNA.
DR EMBL; BC012933; AAH12933.2; -; mRNA.
DR EMBL; BC065287; AAH65287.1; -; mRNA.
DR EMBL; BC087834; AAH87834.1; -; mRNA.
DR EMBL; BC098121; AAH98121.1; ALT_SEQ; mRNA.
DR EMBL; BC099714; AAH99714.1; -; mRNA.
DR EMBL; BC103498; AAI03499.1; -; mRNA.
DR EMBL; BC104483; AAI04484.1; ALT_FRAME; mRNA.
DR EMBL; AF264782; AAG36937.1; ALT_FRAME; mRNA.
DR EMBL; AF151843; AAD34080.1; ALT_INIT; mRNA.
DR EMBL; AK000046; BAA90905.1; ALT_INIT; mRNA.
DR EMBL; AL512763; CAC21680.1; -; mRNA.
DR CCDS; CCDS31623.1; -. [Q4FZB7-1]
DR CCDS; CCDS44660.1; -. [Q4FZB7-2]
DR RefSeq; NP_001287838.1; NM_001300909.1.
DR RefSeq; NP_057112.3; NM_016028.4. [Q4FZB7-2]
DR RefSeq; NP_060105.3; NM_017635.4. [Q4FZB7-1]
DR RefSeq; XP_005274092.2; XM_005274035.3. [Q4FZB7-1]
DR RefSeq; XP_011543393.1; XM_011545091.1.
DR RefSeq; XP_011543395.1; XM_011545093.2.
DR RefSeq; XP_011543396.1; XM_011545094.2.
DR PDB; 3S8P; X-ray; 1.85 A; A/B=63-335.
DR PDB; 5CPR; X-ray; 2.22 A; B=69-335.
DR PDB; 5WBV; X-ray; 2.30 A; A/B=63-335.
DR PDBsum; 3S8P; -.
DR PDBsum; 5CPR; -.
DR PDBsum; 5WBV; -.
DR AlphaFoldDB; Q4FZB7; -.
DR SMR; Q4FZB7; -.
DR BioGRID; 119300; 19.
DR DIP; DIP-48656N; -.
DR IntAct; Q4FZB7; 10.
DR MINT; Q4FZB7; -.
DR STRING; 9606.ENSP00000305899; -.
DR BindingDB; Q4FZB7; -.
DR ChEMBL; CHEMBL2321645; -.
DR GuidetoPHARMACOLOGY; 2717; -.
DR GlyConnect; 2047; 2 N-Linked glycans (1 site).
DR GlyGen; Q4FZB7; 1 site, 4 N-linked glycans (1 site).
DR iPTMnet; Q4FZB7; -.
DR PhosphoSitePlus; Q4FZB7; -.
DR BioMuta; KMT5B; -.
DR DMDM; 332278247; -.
DR EPD; Q4FZB7; -.
DR jPOST; Q4FZB7; -.
DR MassIVE; Q4FZB7; -.
DR MaxQB; Q4FZB7; -.
DR PaxDb; Q4FZB7; -.
DR PeptideAtlas; Q4FZB7; -.
DR PRIDE; Q4FZB7; -.
DR ProteomicsDB; 62098; -. [Q4FZB7-1]
DR ProteomicsDB; 62099; -. [Q4FZB7-2]
DR ProteomicsDB; 62100; -. [Q4FZB7-4]
DR Antibodypedia; 30535; 258 antibodies from 22 providers.
DR DNASU; 51111; -.
DR Ensembl; ENST00000304363.9; ENSP00000305899.4; ENSG00000110066.15. [Q4FZB7-1]
DR Ensembl; ENST00000401547.6; ENSP00000385965.2; ENSG00000110066.15. [Q4FZB7-2]
DR Ensembl; ENST00000405515.5; ENSP00000385640.1; ENSG00000110066.15. [Q4FZB7-2]
DR Ensembl; ENST00000441488.6; ENSP00000411146.2; ENSG00000110066.15. [Q4FZB7-4]
DR Ensembl; ENST00000615954.4; ENSP00000484858.1; ENSG00000110066.15. [Q4FZB7-1]
DR GeneID; 51111; -.
DR KEGG; hsa:51111; -.
DR MANE-Select; ENST00000304363.9; ENSP00000305899.4; NM_017635.5; NP_060105.3.
DR UCSC; uc001onm.2; human. [Q4FZB7-1]
DR CTD; 51111; -.
DR DisGeNET; 51111; -.
DR GeneCards; KMT5B; -.
DR HGNC; HGNC:24283; KMT5B.
DR HPA; ENSG00000110066; Low tissue specificity.
DR MalaCards; KMT5B; -.
DR MIM; 610881; gene.
DR MIM; 617788; phenotype.
DR neXtProt; NX_Q4FZB7; -.
DR OpenTargets; ENSG00000110066; -.
DR PharmGKB; PA134958369; -.
DR VEuPathDB; HostDB:ENSG00000110066; -.
DR eggNOG; KOG2589; Eukaryota.
DR GeneTree; ENSGT00940000156431; -.
DR HOGENOM; CLU_328991_0_0_1; -.
DR InParanoid; Q4FZB7; -.
DR OMA; NRTQSRQ; -.
DR OrthoDB; 236983at2759; -.
DR PhylomeDB; Q4FZB7; -.
DR TreeFam; TF106433; -.
DR BioCyc; MetaCyc:HS12712-MON; -.
DR PathwayCommons; Q4FZB7; -.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR SignaLink; Q4FZB7; -.
DR SIGNOR; Q4FZB7; -.
DR BioGRID-ORCS; 51111; 72 hits in 1082 CRISPR screens.
DR ChiTaRS; KMT5B; human.
DR GeneWiki; SUV420H1; -.
DR GenomeRNAi; 51111; -.
DR Pharos; Q4FZB7; Tchem.
DR PRO; PR:Q4FZB7; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q4FZB7; protein.
DR Bgee; ENSG00000110066; Expressed in cortical plate and 208 other tissues.
DR ExpressionAtlas; Q4FZB7; baseline and differential.
DR Genevisible; Q4FZB7; HS.
DR GO; GO:0000779; C:condensed chromosome, centromeric region; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB.
DR GO; GO:0034772; P:histone H4-K20 dimethylation; IEA:InterPro.
DR GO; GO:0034773; P:histone H4-K20 trimethylation; IBA:GO_Central.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
DR GO; GO:0045830; P:positive regulation of isotype switching; ISS:UniProtKB.
DR CDD; cd19184; SET_KMT5B; 1.
DR Gene3D; 1.10.10.1700; -; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR041938; Hist-Lys_N-MTase_N.
DR InterPro; IPR044424; KMT5B_SET.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR039977; Suv4-20/Set9.
DR InterPro; IPR025790; Suv4-20_animal.
DR PANTHER; PTHR12977; PTHR12977; 1.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS51570; SAM_MT43_SUVAR420_2; 1.
DR PROSITE; PS50280; SET; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator; Chromosome;
KW Disease variant; Intellectual disability; Isopeptide bond; Metal-binding;
KW Methyltransferase; Myogenesis; Nucleus; Reference proteome; Repressor;
KW S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW Transferase; Ubl conjugation; Zinc.
FT CHAIN 1..885
FT /note="Histone-lysine N-methyltransferase KMT5B"
FT /id="PRO_0000281787"
FT DOMAIN 193..308
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT REGION 1..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 363..444
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 590..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 716..740
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 816..850
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 19..36
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..434
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 590..613
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 717..731
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 820..848
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 98
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:24396869,
FT ECO:0000269|PubMed:28114273, ECO:0000269|Ref.14,
FT ECO:0007744|PDB:3S8P, ECO:0007744|PDB:5CPR,
FT ECO:0007744|PDB:5WBV"
FT BINDING 203..206
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:24396869,
FT ECO:0000269|PubMed:28114273, ECO:0000269|Ref.14,
FT ECO:0007744|PDB:3S8P, ECO:0007744|PDB:5CPR,
FT ECO:0007744|PDB:5WBV"
FT BINDING 210
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:24396869,
FT ECO:0000269|PubMed:28114273, ECO:0000269|Ref.14,
FT ECO:0007744|PDB:3S8P, ECO:0007744|PDB:5CPR,
FT ECO:0007744|PDB:5WBV"
FT BINDING 257
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:24396869,
FT ECO:0000269|PubMed:28114273, ECO:0007744|PDB:3S8P,
FT ECO:0007744|PDB:5CPR"
FT BINDING 272..273
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:24396869,
FT ECO:0000269|PubMed:28114273, ECO:0000269|Ref.14,
FT ECO:0007744|PDB:3S8P, ECO:0007744|PDB:5CPR,
FT ECO:0007744|PDB:5WBV"
FT BINDING 275
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24396869,
FT ECO:0000269|PubMed:28114273, ECO:0000269|Ref.14,
FT ECO:0007744|PDB:3S8P, ECO:0007744|PDB:5CPR,
FT ECO:0007744|PDB:5WBV"
FT BINDING 319
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24396869,
FT ECO:0000269|PubMed:28114273, ECO:0000269|Ref.14,
FT ECO:0007744|PDB:3S8P, ECO:0007744|PDB:5CPR,
FT ECO:0007744|PDB:5WBV"
FT BINDING 320
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:24396869,
FT ECO:0000269|PubMed:28114273, ECO:0000269|Ref.14,
FT ECO:0007744|PDB:3S8P, ECO:0007744|PDB:5CPR,
FT ECO:0007744|PDB:5WBV"
FT BINDING 321
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24396869,
FT ECO:0000269|PubMed:28114273, ECO:0000269|Ref.14,
FT ECO:0007744|PDB:3S8P, ECO:0007744|PDB:5CPR,
FT ECO:0007744|PDB:5WBV"
FT BINDING 324
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24396869,
FT ECO:0000269|PubMed:28114273, ECO:0000269|Ref.14,
FT ECO:0007744|PDB:3S8P, ECO:0007744|PDB:5CPR,
FT ECO:0007744|PDB:5WBV"
FT CROSSLNK 555
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT VAR_SEQ 274
FT /note="D -> DLINS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040034"
FT VAR_SEQ 275..885
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040035"
FT VAR_SEQ 392..393
FT /note="TS -> SK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10810093,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_024051"
FT VAR_SEQ 394..885
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10810093,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_024052"
FT VARIANT 9
FT /note="N -> I (in dbSNP:rs2512606)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_047765"
FT VARIANT 187..885
FT /note="Missing (in MRD51)"
FT /evidence="ECO:0000269|PubMed:29276005"
FT /id="VAR_081278"
FT VARIANT 264
FT /note="W -> S (in MRD51; unknown pathological significance;
FT dbSNP:rs1555028104)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080549"
FT VARIANT 513
FT /note="A -> V (in MRD51; unknown pathological significance;
FT dbSNP:rs377163167)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080550"
FT VARIANT 540
FT /note="R -> Q (in MRD51; unknown pathological significance;
FT dbSNP:rs565603169)"
FT /evidence="ECO:0000269|PubMed:28191889"
FT /id="VAR_080551"
FT MUTAGEN 229
FT /note="G->F: Km for H4K20me1rise to 17 uM. 8-fold decrease
FT in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:24396869"
FT MUTAGEN 229
FT /note="G->Y: Abolishes histone methyltransferase activity
FT (H4-K20 specific)."
FT /evidence="ECO:0000269|PubMed:24396869"
FT MUTAGEN 251
FT /note="S->A: Abolishes histone methyltransferase activity
FT (H4-K20 specific)."
FT /evidence="ECO:0000269|PubMed:24396869"
FT MUTAGEN 264
FT /note="W->A: Abolishes histone methyltransferase activity
FT (H4-K20 specific)."
FT /evidence="ECO:0000269|PubMed:24396869"
FT MUTAGEN 281
FT /note="F->A: Abolishes histone methyltransferase activity
FT (H4-K20 specific)."
FT /evidence="ECO:0000269|PubMed:24396869"
FT MUTAGEN 311
FT /note="F->A: Km for H4K20me1rise to 8.5 uM. 3-fold decrease
FT in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:24396869"
FT CONFLICT 74
FT /note="A -> P (in Ref. 4; AAD34080)"
FT /evidence="ECO:0000305"
FT CONFLICT 79
FT /note="E -> G (in Ref. 4; AAD34080)"
FT /evidence="ECO:0000305"
FT CONFLICT 99
FT /note="K -> Q (in Ref. 4; AAD34080)"
FT /evidence="ECO:0000305"
FT CONFLICT 108
FT /note="R -> W (in Ref. 3; AAG36937)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="N -> K (in Ref. 4; AAD34080)"
FT /evidence="ECO:0000305"
FT CONFLICT 135
FT /note="E -> G (in Ref. 4; AAD34080)"
FT /evidence="ECO:0000305"
FT CONFLICT 469
FT /note="K -> E (in Ref. 5; BAA90905)"
FT /evidence="ECO:0000305"
FT CONFLICT 483
FT /note="V -> A (in Ref. 5; BAA90905)"
FT /evidence="ECO:0000305"
FT HELIX 74..93
FT /evidence="ECO:0007829|PDB:3S8P"
FT HELIX 134..147
FT /evidence="ECO:0007829|PDB:3S8P"
FT HELIX 150..157
FT /evidence="ECO:0007829|PDB:3S8P"
FT HELIX 161..167
FT /evidence="ECO:0007829|PDB:3S8P"
FT HELIX 172..187
FT /evidence="ECO:0007829|PDB:3S8P"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:3S8P"
FT STRAND 195..200
FT /evidence="ECO:0007829|PDB:3S8P"
FT STRAND 207..216
FT /evidence="ECO:0007829|PDB:3S8P"
FT STRAND 223..234
FT /evidence="ECO:0007829|PDB:3S8P"
FT HELIX 236..242
FT /evidence="ECO:0007829|PDB:3S8P"
FT TURN 245..247
FT /evidence="ECO:0007829|PDB:3S8P"
FT STRAND 252..255
FT /evidence="ECO:0007829|PDB:3S8P"
FT TURN 256..259
FT /evidence="ECO:0007829|PDB:3S8P"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:3S8P"
FT HELIX 267..270
FT /evidence="ECO:0007829|PDB:3S8P"
FT STRAND 278..285
FT /evidence="ECO:0007829|PDB:3S8P"
FT STRAND 288..295
FT /evidence="ECO:0007829|PDB:3S8P"
FT TURN 309..312
FT /evidence="ECO:0007829|PDB:3S8P"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:3S8P"
FT HELIX 322..327
FT /evidence="ECO:0007829|PDB:3S8P"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:3S8P"
SQ SEQUENCE 885 AA; 99188 MW; 13B0B6E35F751F48 CRC64;
MKWLGESKNM VVNGRRNGGK LSNDHQQNQS KLQHTGKDTL KAGKNAVERR SNRCNGNSGF
EGQSRYVPSS GMSAKELCEN DDLATSLVLD PYLGFQTHKM NTSAFPSRSS RHFSKSDSFS
HNNPVRFRPI KGRQEELKEV IERFKKDEHL EKAFKCLTSG EWARHYFLNK NKMQEKLFKE
HVFIYLRMFA TDSGFEILPC NRYSSEQNGA KIVATKEWKR NDKIELLVGC IAELSEIEEN
MLLRHGENDF SVMYSTRKNC AQLWLGPAAF INHDCRPNCK FVSTGRDTAC VKALRDIEPG
EEISCYYGDG FFGENNEFCE CYTCERRGTG AFKSRVGLPA PAPVINSKYG LRETDKRLNR
LKKLGDSSKN SDSQSVSSNT DADTTQEKNN ATSNRKSSVG VKKNSKSRTL TRQSMSRIPA
SSNSTSSKLT HINNSRVPKK LKKPAKPLLS KIKLRNHCKR LEQKNASRKL EMGNLVLKEP
KVVLYKNLPI KKDKEPEGPA QAAVASGCLT RHAAREHRQN PVRGAHSQGE SSPCTYITRR
SVRTRTNLKE ASDIKLEPNT LNGYKSSVTE PCPDSGEQLQ PAPVLQEEEL AHETAQKGEA
KCHKSDTGMS KKKSRQGKLV KQFAKIEEST PVHDSPGKDD AVPDLMGPHS DQGEHSGTVG
VPVSYTDCAP SPVGCSVVTS DSFKTKDSFR TAKSKKKRRI TRYDAQLILE NNSGIPKLTL
RRRHDSSSKT NDQENDGMNS SKISIKLSKD HDNDNNLYVA KLNNGFNSGS GSSSTKLKIQ
LKRDEENRGS YTEGLHENGV CCSDPLSLLE SRMEVDDYSQ YEEESTDDSS SSEGDEEEDD
YDDDFEDDFI PLPPAKRLRL IVGKDSIDID ISSRRREDQS LRLNA
