ID   KMT5B_RAT               Reviewed;         883 AA.
AC   P0C2N5;
DT   03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2007, sequence version 1.
DT   24-JAN-2024, entry version 108.
DE   RecName: Full=Histone-lysine N-methyltransferase KMT5B {ECO:0000305};
DE   AltName: Full=Lysine-specific methyltransferase 5B {ECO:0000312|RGD:1311637};
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:0000250|UniProtKB:Q4FZB7};
DE   AltName: Full=[histone H4]-lysine20 N-methyltransferase KMT5B {ECO:0000305};
DE            EC=2.1.1.361 {ECO:0000250|UniProtKB:Q4FZB7};
GN   Name=Kmt5b {ECO:0000312|RGD:1311637}; Synonyms=Suv420h1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
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. In vitro also methylates
CC       unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes (By
CC       similarity). H4 'Lys-20' trimethylation represents a specific tag for
CC       epigenetic transcriptional repression. Mainly functions in pericentric
CC       heterochromatin regions, thereby playing a central role in the
CC       establishment of constitutive heterochromatin in these regions. KMT5B
CC       is targeted to histone H3 via its interaction with RB1 family proteins
CC       (RB1, RBL1 and RBL2) (By similarity). Plays a role in myogenesis by
CC       regulating the expression of target genes, such as EID3. Facilitates
CC       TP53BP1 foci formation upon DNA damage and proficient non-homologous
CC       end-joining (NHEJ)-directed DNA repair by catalyzing the di- and
CC       trimethylation of 'Lys-20' of histone H4 (By similarity). May play a
CC       role in class switch reconbination by catalyzing the di- and
CC       trimethylation of 'Lys-20' of histone H4 (By similarity).
CC       {ECO:0000250|UniProtKB:Q3U8K7, ECO:0000250|UniProtKB:Q4FZB7}.
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:0000250|UniProtKB:Q4FZB7};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60349;
CC         Evidence={ECO:0000250|UniProtKB:Q4FZB7};
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:0000250|UniProtKB:Q4FZB7};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61993;
CC         Evidence={ECO:0000250|UniProtKB:Q4FZB7};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:60344, Rhea:RHEA-COMP:15554, Rhea:RHEA-COMP:15555,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.361;
CC         Evidence={ECO:0000250|UniProtKB:Q4FZB7};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60345;
CC         Evidence={ECO:0000250|UniProtKB:Q4FZB7};
CC   -!- ACTIVITY REGULATION: Inhibited by 6,7-Dichloro-N-cyclopentyl-4-
CC       (pyridin-4-yl)phthalazin-1-amine (A-196). A-196 is competitive with the
CC       histone peptide substrate H4K20me1 but non competitive with S-adenosyl-
CC       L-methionine. {ECO:0000250|UniProtKB:Q4FZB7}.
CC   -!- SUBUNIT: Homodimer (By similarity). Interacts with HP1 proteins CBX1,
CC       CBX3 and CBX5. Interacts with RB1 family proteins RB1, RBL1 and RBL2
CC       (By similarity). Interacts (via C-terminus) with FRG1 (By similarity).
CC       {ECO:0000250, ECO:0000250|UniProtKB:Q4FZB7}.
CC   -!- SUBCELLULAR LOCATION: Nucleus. Chromosome {ECO:0000250}.
CC       Note=Associated with pericentric heterochromatin. CBX1 and CBX5 are
CC       required for the localization to pericentric heterochromatin (By
CC       similarity). {ECO:0000250}.
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}.
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DR   EMBL; AABR03001123; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_001101982.1; NM_001108512.1.
DR   AlphaFoldDB; P0C2N5; -.
DR   SMR; P0C2N5; -.
DR   STRING; 10116.ENSRNOP00000022486; -.
DR   iPTMnet; P0C2N5; -.
DR   PhosphoSitePlus; P0C2N5; -.
DR   PaxDb; 10116-ENSRNOP00000022486; -.
DR   Ensembl; ENSRNOT00000022486.7; ENSRNOP00000022486.5; ENSRNOG00000016790.7.
DR   Ensembl; ENSRNOT00055036191; ENSRNOP00055029402; ENSRNOG00055021177.
DR   Ensembl; ENSRNOT00060056400; ENSRNOP00060046602; ENSRNOG00060032548.
DR   Ensembl; ENSRNOT00065054600; ENSRNOP00065044908; ENSRNOG00065031695.
DR   GeneID; 361688; -.
DR   KEGG; rno:361688; -.
DR   UCSC; RGD:1311637; rat.
DR   AGR; RGD:1311637; -.
DR   CTD; 51111; -.
DR   RGD; 1311637; Kmt5b.
DR   eggNOG; KOG2589; Eukaryota.
DR   GeneTree; ENSGT00940000156431; -.
DR   HOGENOM; CLU_328991_0_0_1; -.
DR   InParanoid; P0C2N5; -.
DR   OMA; MGETKNM; -.
DR   OrthoDB; 5396777at2759; -.
DR   PhylomeDB; P0C2N5; -.
DR   TreeFam; TF106433; -.
DR   Reactome; R-RNO-3214841; PKMTs methylate histone lysines.
DR   PRO; PR:P0C2N5; -.
DR   Proteomes; UP000002494; Chromosome 1.
DR   Bgee; ENSRNOG00000016790; Expressed in thymus and 20 other cell types or tissues.
DR   GO; GO:0000779; C:condensed chromosome, centromeric region; ISO:RGD.
DR   GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR   GO; GO:0042799; F:histone H4K20 methyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0140944; F:histone H4K20 monomethyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0140941; F:histone H4K20me methyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0042054; F:histone methyltransferase activity; ISS: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:0006338; P:chromatin remodeling; ISO:RGD.
DR   GO; GO:0006281; P:DNA repair; ISS:UniProtKB.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
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; ISS: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; Histone-lysine N-methyltransferase; 1.
DR   Gene3D; 2.170.270.10; SET domain; 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:SF12; HISTONE-LYSINE N-METHYLTRANSFERASE KMT5B; 1.
DR   PANTHER; PTHR12977; SUPPRESSOR OF VARIEGATION 4-20-RELATED; 1.
DR   Pfam; PF00856; SET; 1.
DR   SMART; SM00317; SET; 1.
DR   SUPFAM; SSF82199; SET domain; 1.
DR   PROSITE; PS51570; SAM_MT43_SUVAR420_2; 1.
DR   PROSITE; PS50280; SET; 1.
DR   Genevisible; P0C2N5; RN.
PE   3: Inferred from homology;
KW   Chromatin regulator; Chromosome; 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..883
FT                   /note="Histone-lysine N-methyltransferase KMT5B"
FT                   /id="PRO_0000281789"
FT   DOMAIN          193..308
FT                   /note="SET"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   REGION          1..66
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          103..124
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          363..435
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          515..740
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          760..779
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          812..848
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        12..35
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        37..55
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        103..121
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        368..432
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        524..542
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        588..612
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        619..633
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        657..687
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        715..734
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        760..775
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        814..846
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:0000250|UniProtKB:Q4FZB7"
FT   BINDING         203..206
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q4FZB7"
FT   BINDING         210
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q4FZB7"
FT   BINDING         257
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q4FZB7"
FT   BINDING         272..273
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q4FZB7"
FT   BINDING         275
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q4FZB7"
FT   BINDING         319
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q4FZB7"
FT   BINDING         320
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q4FZB7"
FT   BINDING         321
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q4FZB7"
FT   BINDING         324
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q4FZB7"
FT   CROSSLNK        555
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q4FZB7"
SQ   SEQUENCE   883 AA;  98668 MW;  1C5EAE2B39D2542F CRC64;
     MKWLGDSKNM VVNGRRNGSK LSNDHQQNQS KLQHAGKDAL KTGRNAVERR PNRCHGNSGF
     EGQSRYVPSS GMSAKELCEN DDLATSLVLD PYLGFQTHKM NTSAFPSRSS RHISKADSFS
     HNNPMRFRPI KGRQEELKEV IERFKKDEHL EKAFKCLTSG EWARHYFLNK NKMQEKLFKE
     HVFIYLRMFA TDSGFEILPC NRYSSEQNGA KIVATKEWKR NDKIELLVGC IAELSEIEEN
     MLLRHGENDF SVMYSTRKNC AQLWLGPAAF INHDCRPNCK FVSTGRDTAC VKALRDIEPG
     EEISCYYGDG FFGENNEFCE CYTCERRGTG AFKSRVGLPA PAPVINSKYG LRETDKRLNR
     LKKLGDSSKS SDSQSVSSNT DADTTQEKDN ATSNRKSSVG VKKNSKSRAL TRQSMPRVPA
     ASNSTSPKLV HMNNSRVPKK LRKPAKPLLS KIKLRNHCKR LDQKSTSRKL EMGNLVLKEP
     KVVLYKNLPI KKEREAEGPV HAAVGSGCLT RHAAREHRQN PGRGAHSQGD SLPCTYTTRR
     SLRTRTGLKE TTDIKLAPSP LDGYKNGILE PYPDSGQQPT PEVLEELAPE TALREEASQE
     CPKSDSCPSR KKFRQGKPVK HLAKTEDCSP EHSFPGKDGL PDLPGPHPDQ GEPSGTVRVP
     VSYTDSAPSP VGCSIVTPDS FTTKDSFRTA QSKKKRRVTR YDAQLILENS SGIPKLTLRR
     RHDSSSKTND HESDSVNSSK ISIKLSKDHE SDSNLYVAKL SNGVSSGPGS SSTKLKIQLK
     RDEESRGPCA EGLHENGVCC SDPLSLLESQ MEVDDYSQYE EDSTDDSSSS EGEEEEEDCE
     DDFDDDFIPL PPAKRLRLIV GKDSIDIDIS SRRREDQSLR LNA
//