KMT5B_RAT
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 03-AUG-2022, entry version 100.
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; P0C2N5; -.
DR PRIDE; P0C2N5; -.
DR Ensembl; ENSRNOT00000022486; ENSRNOP00000022486; ENSRNOG00000016790.
DR GeneID; 361688; -.
DR KEGG; rno:361688; -.
DR UCSC; RGD:1311637; rat.
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; GETKNMV; -.
DR OrthoDB; 236983at2759; -.
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 tissues.
DR Genevisible; P0C2N5; RN.
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 methyltransferase activity (H4-K20 specific); ISS:UniProtKB.
DR GO; GO:0018024; F:histone-lysine N-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:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; ISS: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:0016571; P:histone methylation; ISO:RGD.
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; -; 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 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
