CLR4_SCHPO
ID CLR4_SCHPO Reviewed; 490 AA.
AC O60016; O74565;
DT 08-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 08-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-9 specific;
DE EC=2.1.1.355 {ECO:0000269|PubMed:11283354};
DE EC=2.1.1.366 {ECO:0000269|PubMed:30051891};
DE EC=2.1.1.367 {ECO:0000269|PubMed:10949293, ECO:0000269|PubMed:11283354};
DE AltName: Full=Cryptic loci regulator 4;
DE AltName: Full=Histone H3-K9 methyltransferase;
DE Short=H3-K9-HMTase;
DE Short=HKMT;
DE AltName: Full=Lysine N-methyltransferase 1;
DE AltName: Full=Protein lysine methyltransferase clr4 {ECO:0000303|PubMed:28143796};
DE Short=PKMT;
GN Name=clr4; Synonyms=kmt1; ORFNames=SPBC428.08c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9620780; DOI=10.1038/566;
RA Ivanova A.V., Bonaduce M.J., Ivanov S.V., Klar A.J.S.;
RT "The chromo and SET domains of the Clr4 protein are essential for silencing
RT in fission yeast.";
RL Nat. Genet. 19:192-195(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=SP813;
RA Lord P.;
RL Thesis (1998), University of Edinburgh, United Kingdom.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [4]
RP PARTIAL PROTEIN SEQUENCE, IDENTIFICATION IN THE RIK1-ASSOCIATED E3
RP UBIQUITIN LIGASE COMPLEX, AND FUNCTION.
RX PubMed=16024659; DOI=10.1101/gad.1328005;
RA Horn P.J., Bastie J.-N., Peterson C.L.;
RT "A Rik1-associated, cullin-dependent E3 ubiquitin ligase is essential for
RT heterochromatin formation.";
RL Genes Dev. 19:1705-1714(2005).
RN [5]
RP PROTEIN SEQUENCE OF 64-85; 127-150; 190-205; 371-406; 429-455 AND 486-490,
RP AND INTERACTION WITH CUL4.
RX PubMed=16127433; DOI=10.1038/ncb1300;
RA Jia S., Kobayashi R., Grewal S.I.S.;
RT "Ubiquitin ligase component Cul4 associates with Clr4 histone
RT methyltransferase to assemble heterochromatin.";
RL Nat. Cell Biol. 7:1007-1013(2005).
RN [6]
RP FUNCTION.
RX PubMed=8138176; DOI=10.1093/genetics/136.1.53;
RA Ekwall K., Ruusala T.;
RT "Mutations in rik1, clr2, clr3 and clr4 genes asymmetrically derepress the
RT silent mating-type loci in fission yeast.";
RL Genetics 136:53-64(1994).
RN [7]
RP CATALYTIC ACTIVITY.
RX PubMed=10949293; DOI=10.1038/35020506;
RA Rea S., Eisenhaber F., O'Carroll D., Strahl B.D., Sun Z.-W., Schmid M.,
RA Opravil S., Mechtler K., Ponting C.P., Allis C.D., Jenuwein T.;
RT "Regulation of chromatin structure by site-specific histone H3
RT methyltransferases.";
RL Nature 406:593-599(2000).
RN [8]
RP FUNCTION.
RX PubMed=11242054; DOI=10.1038/35065138;
RA Bannister A.J., Zegerman P., Partridge J.F., Miska E.A., Thomas J.O.,
RA Allshire R.C., Kouzarides T.;
RT "Selective recognition of methylated lysine 9 on histone H3 by the HP1
RT chromo domain.";
RL Nature 410:120-124(2001).
RN [9]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF TRP-31; TRP-41; ARG-320; GLY-378 AND
RP GLY-486.
RX PubMed=11283354; DOI=10.1126/science.1060118;
RA Nakayama J., Rice J.C., Strahl B.D., Allis C.D., Grewal S.I.S.;
RT "Role of histone H3 lysine 9 methylation in epigenetic control of
RT heterochromatin assembly.";
RL Science 292:110-113(2001).
RN [10]
RP SUBUNIT.
RX PubMed=17114925; DOI=10.4161/rna.2.3.2131;
RA Hong E.J., Villen J., Gerace E.L., Gygi S.P., Moazed D.;
RT "A cullin E3 ubiquitin ligase complex associates with Rik1 and the Clr4
RT histone H3-K9 methyltransferase and is required for RNAi-mediated
RT heterochromatin formation.";
RL RNA Biol. 2:106-111(2005).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18345014; DOI=10.1038/nsmb.1406;
RA Zhang K., Mosch K., Fischle W., Grewal S.I.;
RT "Roles of the Clr4 methyltransferase complex in nucleation, spreading and
RT maintenance of heterochromatin.";
RL Nat. Struct. Mol. Biol. 15:381-388(2008).
RN [13]
RP FUNCTION.
RX PubMed=20705239; DOI=10.1016/j.molcel.2010.07.017;
RA Gerace E.L., Halic M., Moazed D.;
RT "The methyltransferase activity of Clr4Suv39h triggers RNAi independently
RT of histone H3K9 methylation.";
RL Mol. Cell 39:360-372(2010).
RN [14]
RP FUNCTION.
RX PubMed=21224386; DOI=10.1074/jbc.m110.143198;
RA Haldar S., Saini A., Nanda J.S., Saini S., Singh J.;
RT "Role of Swi6/HP1 self-association-mediated recruitment of Clr4/Suv39 in
RT establishment and maintenance of heterochromatin in fission yeast.";
RL J. Biol. Chem. 286:9308-9320(2011).
RN [15]
RP FUNCTION, AND INTERACTION WITH MLO3.
RX PubMed=21436456; DOI=10.1126/science.1198712;
RA Zhang K., Fischer T., Porter R.L., Dhakshnamoorthy J., Zofall M., Zhou M.,
RA Veenstra T., Grewal S.I.;
RT "Clr4/Suv39 and RNA quality control factors cooperate to trigger RNAi and
RT suppress antisense RNA.";
RL Science 331:1624-1627(2011).
RN [16]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=28143796; DOI=10.1016/j.biochi.2017.01.013;
RA Kusevic D., Kudithipudi S., Iglesias N., Moazed D., Jeltsch A.;
RT "Clr4 specificity and catalytic activity beyond H3K9 methylation.";
RL Biochimie 135:83-88(2017).
RN [17]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31468675; DOI=10.15252/embr.201948111;
RA Oya E., Nakagawa R., Yoshimura Y., Tanaka M., Nishibuchi G., Machida S.,
RA Shirai A., Ekwall K., Kurumizaka H., Tagami H., Nakayama J.I.;
RT "H3K14 ubiquitylation promotes H3K9 methylation for heterochromatin
RT assembly.";
RL EMBO Rep. 20:E48111-E48111(2019).
RN [18]
RP STRUCTURE BY NMR OF 2-69.
RX PubMed=11273706; DOI=10.1006/jmbi.2001.4515;
RA Horita D.A., Ivanova A.V., Altieri A.S., Klar A.J., Byrd R.A.;
RT "Solution structure, domain features, and structural implications of
RT mutants of the chromo domain from the fission yeast histone
RT methyltransferase Clr4.";
RL J. Mol. Biol. 307:861-870(2001).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 192-490 IN COMPLEX WITH ZINC IONS.
RX PubMed=12389037; DOI=10.1038/nsb860;
RA Min J., Zhang X., Cheng X., Grewal S.I.S., Xu R.M.;
RT "Structure of the SET domain histone lysine methyltransferase Clr4.";
RL Nat. Struct. Biol. 9:828-832(2002).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) OF 192-490 IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE AND ZINC IONS, METHYLATION AT LYS-127; LYS-455
RP AND LYS-464, AND MUTAGENESIS OF TYR-451 AND LYS-455.
RX PubMed=30051891; DOI=10.1038/s41586-018-0398-2;
RA Iglesias N., Currie M.A., Jih G., Paulo J.A., Siuti N., Kalocsay M.,
RA Gygi S.P., Moazed D.;
RT "Automethylation-induced conformational switch in Clr4 (Suv39h) maintains
RT epigenetic stability.";
RL Nature 560:504-508(2018).
CC -!- FUNCTION: Histone methyltransferase which contributes to the
CC establishment of heterochromatin by specifically methylating histone H3
CC to form H3K9me (PubMed:16024659, PubMed:8138176). Part of the Clr4
CC methyltransferase complex (ClrC). ClrC preferentially ubiquitylates
CC H3K14 and ClrC-mediated H3 ubiquitination promotes clr4
CC methyltransferase activity (PubMed:31468675). Clr4 functions as a
CC reader and writer of H3K9 methylation. It sets the H3K9me mark and
CC afterwards this H3K9me mark is recognized by the chromodomains of clr4
CC and swi6/HP1, which then recruit additional clr4 leading to the
CC methylation of neighboring nucleosomes (PubMed:11242054,
CC PubMed:18345014, PubMed:21224386). H3K9me represents a specific tag for
CC epigenetic transcriptional repression by recruiting swi6/HP1 to
CC methylated histones which leads to transcriptional silencing within
CC centromeric heterochromatin, telomeres, ribosomal DNA repeats, and the
CC silent mating-type region (PubMed:16024659, PubMed:8138176). Clr4
CC methyltransferase activity promotes the assembly of a tripartite
CC complex composed of ClrC and complexes involved in siRNA generation
CC (PubMed:20705239). Apart from H3K9, methylates also non-histone
CC proteins such as mlo3 (PubMed:21436456, PubMed:28143796). Interacts
CC with mlo3 to promote the processing of centromeric and antisense RNAs
CC (PubMed:21436456). {ECO:0000269|PubMed:11242054,
CC ECO:0000269|PubMed:16024659, ECO:0000269|PubMed:18345014,
CC ECO:0000269|PubMed:20705239, ECO:0000269|PubMed:21224386,
CC ECO:0000269|PubMed:21436456, ECO:0000269|PubMed:28143796,
CC ECO:0000269|PubMed:31468675, ECO:0000269|PubMed:8138176}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) +
CC N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60276, Rhea:RHEA-COMP:15538, Rhea:RHEA-
CC COMP:15546, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.355;
CC Evidence={ECO:0000269|PubMed:11283354};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine
CC = H(+) + N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60284, Rhea:RHEA-COMP:15541, Rhea:RHEA-
CC COMP:15542, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976;
CC Evidence={ECO:0000269|PubMed:11283354, ECO:0000269|PubMed:30051891};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-
CC methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3]
CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60288, Rhea:RHEA-
CC COMP:15538, Rhea:RHEA-COMP:15541, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961,
CC ChEBI:CHEBI:61976; EC=2.1.1.366;
CC Evidence={ECO:0000269|PubMed:30051891};
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:0000269|PubMed:28143796};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-methionine = H(+)
CC + N(6),N(6)-dimethyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:54196, Rhea:RHEA-COMP:13053, Rhea:RHEA-COMP:13827,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976;
CC Evidence={ECO:0000269|PubMed:28143796};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6),N(6)-dimethyl-L-lysyl-[protein] + S-adenosyl-L-methionine
CC = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:54200, Rhea:RHEA-COMP:13826, Rhea:RHEA-
CC COMP:13827, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61961, ChEBI:CHEBI:61976;
CC Evidence={ECO:0000269|PubMed:28143796};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:60280, Rhea:RHEA-COMP:15542, Rhea:RHEA-COMP:15546,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.367;
CC Evidence={ECO:0000269|PubMed:10949293, ECO:0000269|PubMed:11283354};
CC -!- ACTIVITY REGULATION: An internal loop (autoregulatory loop) inhibits
CC the catalytic activity of the enzyme by blocking the histone H3K9
CC substrate-binding pocket. Autocatalytic methylation of specific lysine
CC residues in this loop promote a conformational switch that enhances the
CC H3K9me activity of clr4. {ECO:0000269|PubMed:30051891}.
CC -!- SUBUNIT: Component of the Clr4 methyltransferase complex (ClrC)
CC composed of at least clr4, rik1, pcu4, rbx1, raf1 and raf2. The cullin
CC pcu4, rik1, raf1, raf2 and the ring-box protein rbx1 are components of
CC an E3 ubiquitin ligase, whose activity is essential for heterochromatin
CC assembly (PubMed:16024659, PubMed:16127433, PubMed:17114925,
CC PubMed:12389037). Interacts directly with pcu4 (PubMed:16127433).
CC Interacts with mlo3 (PubMed:21436456). {ECO:0000269|PubMed:12389037,
CC ECO:0000269|PubMed:16024659, ECO:0000269|PubMed:16127433,
CC ECO:0000269|PubMed:17114925, ECO:0000269|PubMed:21436456}.
CC -!- INTERACTION:
CC O60016; O14122: pcu4; NbExp=3; IntAct=EBI-354657, EBI-904890;
CC O60016; Q10426: rik1; NbExp=3; IntAct=EBI-354657, EBI-1111936;
CC O60016; O94276: SPBP8B7.28c; NbExp=2; IntAct=EBI-354657, EBI-2651917;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16823372,
CC ECO:0000269|PubMed:18345014}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, spindle pole body {ECO:0000269|PubMed:16823372}.
CC Chromosome {ECO:0000269|PubMed:18345014, ECO:0000305|PubMed:16823372}.
CC -!- DOMAIN: The chromodomain serves to recognize and bind to H3K9me.
CC {ECO:0000269|PubMed:18345014}.
CC -!- DOMAIN: In the pre-SET domain, Cys residues bind 3 zinc ions that are
CC arranged in a triangular cluster; some of these Cys residues contribute
CC to the binding of two zinc ions within the cluster.
CC -!- PTM: Autocatalytic methylation of specific lysine residues in an
CC internal loop (autoregulatory loop) promote a conformational switch
CC that enhances the H3K9me activity of clr4.
CC {ECO:0000269|PubMed:30051891}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family. Suvar3-9
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; AF061854; AAC18302.1; -; Genomic_DNA.
DR EMBL; AJ007840; CAA07709.1; -; Genomic_DNA.
DR EMBL; CU329671; CAA22283.1; -; Genomic_DNA.
DR PIR; T43700; T43700.
DR PIR; T43745; T43745.
DR RefSeq; NP_595186.1; NM_001021094.2.
DR PDB; 1G6Z; NMR; -; A=2-69.
DR PDB; 1MVH; X-ray; 2.30 A; A=192-490.
DR PDB; 1MVX; X-ray; 3.00 A; A=192-490.
DR PDB; 6BOX; X-ray; 2.41 A; A/B=192-490.
DR PDB; 6BP4; X-ray; 2.77 A; A/B=192-490.
DR PDBsum; 1G6Z; -.
DR PDBsum; 1MVH; -.
DR PDBsum; 1MVX; -.
DR PDBsum; 6BOX; -.
DR PDBsum; 6BP4; -.
DR AlphaFoldDB; O60016; -.
DR SMR; O60016; -.
DR BioGRID; 277343; 308.
DR DIP; DIP-32588N; -.
DR IntAct; O60016; 8.
DR MINT; O60016; -.
DR STRING; 4896.SPBC428.08c.1; -.
DR iPTMnet; O60016; -.
DR MaxQB; O60016; -.
DR PaxDb; O60016; -.
DR PRIDE; O60016; -.
DR EnsemblFungi; SPBC428.08c.1; SPBC428.08c.1:pep; SPBC428.08c.
DR GeneID; 2540825; -.
DR KEGG; spo:SPBC428.08c; -.
DR PomBase; SPBC428.08c; clr4.
DR VEuPathDB; FungiDB:SPBC428.08c; -.
DR eggNOG; KOG1082; Eukaryota.
DR HOGENOM; CLU_020840_8_2_1; -.
DR InParanoid; O60016; -.
DR OMA; EVDDEPC; -.
DR PhylomeDB; O60016; -.
DR EvolutionaryTrace; O60016; -.
DR PRO; PR:O60016; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0099115; C:chromosome, subtelomeric region; NAS:PomBase.
DR GO; GO:0043494; C:CLRC complex; IDA:PomBase.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0031934; C:mating-type region heterochromatin; NAS:PomBase.
DR GO; GO:0005634; C:nucleus; HDA:PomBase.
DR GO; GO:0005721; C:pericentric heterochromatin; TAS:PomBase.
DR GO; GO:0005816; C:spindle pole body; IEA:UniProtKB-SubCell.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:PomBase.
DR GO; GO:0042054; F:histone methyltransferase activity; IBA:GO_Central.
DR GO; GO:0046974; F:histone methyltransferase activity (H3-K9 specific); IDA:UniProtKB.
DR GO; GO:0140566; F:histone reader activity; EXP:PomBase.
DR GO; GO:0008168; F:methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:PomBase.
DR GO; GO:0003727; F:single-stranded RNA binding; IDA:PomBase.
DR GO; GO:0043130; F:ubiquitin binding; EXP:PomBase.
DR GO; GO:0061649; F:ubiquitin modification-dependent histone binding; IPI:PomBase.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007535; P:donor selection; IMP:PomBase.
DR GO; GO:0070314; P:G1 to G0 transition; IMP:PomBase.
DR GO; GO:0051567; P:histone H3-K9 methylation; IEA:UniProt.
DR GO; GO:0016571; P:histone methylation; IBA:GO_Central.
DR GO; GO:0045141; P:meiotic telomere clustering; IMP:PomBase.
DR GO; GO:0031508; P:pericentric heterochromatin assembly; IMP:PomBase.
DR GO; GO:0090053; P:positive regulation of pericentric heterochromatin assembly; IMP:CACAO.
DR GO; GO:0030466; P:silent mating-type cassette heterochromatin assembly; IMP:PomBase.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR016197; Chromo-like_dom_sf.
DR InterPro; IPR000953; Chromo/chromo_shadow_dom.
DR InterPro; IPR023780; Chromo_domain.
DR InterPro; IPR023779; Chromodomain_CS.
DR InterPro; IPR011381; Histone_H3-K9_MeTrfase.
DR InterPro; IPR003616; Post-SET_dom.
DR InterPro; IPR007728; Pre-SET_dom.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR Pfam; PF00385; Chromo; 1.
DR Pfam; PF05033; Pre-SET; 1.
DR Pfam; PF00856; SET; 1.
DR PIRSF; PIRSF009343; SUV39_SET; 1.
DR SMART; SM00298; CHROMO; 1.
DR SMART; SM00508; PostSET; 1.
DR SMART; SM00468; PreSET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF54160; SSF54160; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS00598; CHROMO_1; 1.
DR PROSITE; PS50013; CHROMO_2; 1.
DR PROSITE; PS50868; POST_SET; 1.
DR PROSITE; PS50867; PRE_SET; 1.
DR PROSITE; PS50280; SET; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromatin regulator; Chromosome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Metal-binding; Methylation; Methyltransferase;
KW Nucleus; Reference proteome; S-adenosyl-L-methionine; Transferase; Zinc.
FT CHAIN 1..490
FT /note="Histone-lysine N-methyltransferase, H3 lysine-9
FT specific"
FT /id="PRO_0000186063"
FT DOMAIN 8..69
FT /note="Chromo"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00053"
FT DOMAIN 258..325
FT /note="Pre-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00157"
FT DOMAIN 328..452
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 473..489
FT /note="Post-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT REGION 61..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 150..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 453..472
FT /note="Autoregulatory loop"
FT /evidence="ECO:0000305|PubMed:30051891"
FT COMPBIAS 103..117
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 118..133
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 150..169
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 170..190
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 260
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:12389037,
FT ECO:0000269|PubMed:30051891"
FT BINDING 260
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:12389037,
FT ECO:0000269|PubMed:30051891"
FT BINDING 262
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:12389037,
FT ECO:0000269|PubMed:30051891"
FT BINDING 268
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:12389037,
FT ECO:0000269|PubMed:30051891"
FT BINDING 268
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:12389037,
FT ECO:0000269|PubMed:30051891"
FT BINDING 276
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:12389037,
FT ECO:0000269|PubMed:30051891"
FT BINDING 278
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:12389037,
FT ECO:0000269|PubMed:30051891"
FT BINDING 307
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:12389037,
FT ECO:0000269|PubMed:30051891"
FT BINDING 307
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:12389037,
FT ECO:0000269|PubMed:30051891"
FT BINDING 311
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:12389037,
FT ECO:0000269|PubMed:30051891"
FT BINDING 313
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:12389037,
FT ECO:0000269|PubMed:30051891"
FT BINDING 317
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:12389037,
FT ECO:0000269|PubMed:30051891"
FT BINDING 338..340
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:30051891"
FT BINDING 381
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 406
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 407..410
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:30051891"
FT BINDING 412
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000269|PubMed:30051891"
FT BINDING 477..478
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:30051891"
FT BINDING 477
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000269|PubMed:30051891"
FT BINDING 479
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000269|PubMed:30051891"
FT BINDING 484
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000269|PubMed:30051891"
FT MOD_RES 127
FT /note="N6,N6,N6-trimethyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:30051891"
FT MOD_RES 127
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:30051891"
FT MOD_RES 455
FT /note="N6,N6,N6-trimethyllysine; by autocatalysis;
FT alternate"
FT /evidence="ECO:0000269|PubMed:30051891"
FT MOD_RES 455
FT /note="N6,N6-dimethyllysine; by autocatalysis; alternate"
FT /evidence="ECO:0000269|PubMed:30051891"
FT MOD_RES 455
FT /note="N6-methyllysine; by autocatalysis; alternate"
FT /evidence="ECO:0000269|PubMed:30051891"
FT MOD_RES 464
FT /note="N6-methyllysine"
FT /evidence="ECO:0000269|PubMed:30051891"
FT MUTAGEN 31
FT /note="W->G: Weak effect on methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11283354"
FT MUTAGEN 41
FT /note="W->G: Weak effect on methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11283354"
FT MUTAGEN 320
FT /note="R->H: Abolishes methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11283354"
FT MUTAGEN 378
FT /note="G->S: Abolishes methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11283354"
FT MUTAGEN 451
FT /note="Y->N: Abolishes methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:30051891"
FT MUTAGEN 455
FT /note="K->R: Greatly diminishes Clr4 automethylation and
FT causes hyperactivity towards histone H3K9."
FT /evidence="ECO:0000269|PubMed:30051891"
FT MUTAGEN 486
FT /note="G->D: Abolishes methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11283354"
FT CONFLICT 19
FT /note="D -> G (in Ref. 1; AAC18302)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="Missing (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 437
FT /note="A -> G (in Ref. 1; AAC18302)"
FT /evidence="ECO:0000305"
FT STRAND 14..17
FT /evidence="ECO:0007829|PDB:1G6Z"
FT STRAND 26..29
FT /evidence="ECO:0007829|PDB:1G6Z"
FT TURN 32..35
FT /evidence="ECO:0007829|PDB:1G6Z"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:1G6Z"
FT HELIX 44..47
FT /evidence="ECO:0007829|PDB:1G6Z"
FT HELIX 51..61
FT /evidence="ECO:0007829|PDB:1G6Z"
FT TURN 62..65
FT /evidence="ECO:0007829|PDB:1G6Z"
FT HELIX 196..214
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 216..219
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:6BOX"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:1MVH"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 265..268
FT /evidence="ECO:0007829|PDB:1MVH"
FT TURN 273..275
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 302..305
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 309..313
FT /evidence="ECO:0007829|PDB:6BOX"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 330..334
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 336..346
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 353..356
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 360..363
FT /evidence="ECO:0007829|PDB:1MVH"
FT HELIX 364..371
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 382..385
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 394..397
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 399..402
FT /evidence="ECO:0007829|PDB:1MVH"
FT HELIX 404..407
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 415..423
FT /evidence="ECO:0007829|PDB:1MVH"
FT STRAND 432..439
FT /evidence="ECO:0007829|PDB:1MVH"
FT TURN 452..454
FT /evidence="ECO:0007829|PDB:6BOX"
FT STRAND 455..458
FT /evidence="ECO:0007829|PDB:1MVH"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:6BP4"
SQ SEQUENCE 490 AA; 55918 MW; 53C3EC87BCBA51FF CRC64;
MSPKQEEYEV ERIVDEKLDR NGAVKLYRIR WLNYSSRSDT WEPPENLSGC SAVLAEWKRR
KRRLKGSNSD SDSPHHASNP HPNSRQKHQH QTSKSVPRSQ RFSRELNVKK ENKKVFSSQT
TKRQSRKQST ALTTNDTSII LDDSLHTNSK KLGKTRNEVK EESQKRELVS NSIKEATSPK
TSSILTKPRN PSKLDSYTHL SFYEKRELFR KKLREIEGPE VTLVNEVDDE PCPSLDFQFI
SQYRLTQGVI PPDPNFQSGC NCSSLGGCDL NNPSRCECLD DLDEPTHFAY DAQGRVRADT
GAVIYECNSF CSCSMECPNR VVQRGRTLPL EIFKTKEKGW GVRSLRFAPA GTFITCYLGE
VITSAEAAKR DKNYDDDGIT YLFDLDMFDD ASEYTVDAQN YGDVSRFFNH SCSPNIAIYS
AVRNHGFRTI YDLAFFAIKD IQPLEELTFD YAGAKDFSPV QSQKSQQNRI SKLRRQCKCG
SANCRGWLFG
