UniProt functional annotation for O60016



	UniProt functional annotation for O60016

UniProt code: O60016.

Organism: Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).

Taxonomy: Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina; Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae; Schizosaccharomyces.

Function: Histone methyltransferase which contributes to the establishment of heterochromatin by specifically methylating histone H3 to form H3K9me (PubMed:16024659, PubMed:8138176). Part of the Clr4 methyltransferase complex (ClrC). ClrC preferentially ubiquitylates H3K14 and ClrC-mediated H3 ubiquitination promotes clr4 methyltransferase activity (PubMed:31468675). Clr4 functions as a reader and writer of H3K9 methylation. It sets the H3K9me mark and afterwards this H3K9me mark is recognized by the chromodomains of clr4 and swi6/HP1, which then recruit additional clr4 leading to the methylation of neighboring nucleosomes (PubMed:11242054, PubMed:18345014, PubMed:21224386). H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting swi6/HP1 to methylated histones which leads to transcriptional silencing within centromeric heterochromatin, telomeres, ribosomal DNA repeats, and the silent mating-type region (PubMed:16024659, PubMed:8138176). Clr4 methyltransferase activity promotes the assembly of a tripartite complex composed of ClrC and complexes involved in siRNA generation (PubMed:20705239). Apart from H3K9, methylates also non-histone proteins such as mlo3 (PubMed:21436456, PubMed:28143796). Interacts with mlo3 to promote the processing of centromeric and antisense RNAs (PubMed:21436456). {ECO:0000269|PubMed:11242054, ECO:0000269|PubMed:16024659, ECO:0000269|PubMed:18345014, ECO:0000269|PubMed:20705239, ECO:0000269|PubMed:21224386, ECO:0000269|PubMed:21436456, ECO:0000269|PubMed:28143796, ECO:0000269|PubMed:31468675, ECO:0000269|PubMed:8138176}.

Catalytic activity: Reaction=L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + 3 S-adenosyl-L- homocysteine; Xref=Rhea:RHEA:60276, Rhea:RHEA-COMP:15538, Rhea:RHEA- COMP:15546, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.355; Evidence={ECO:0000269|PubMed:11283354};

Catalytic activity: Reaction=L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = H(+) + N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60280, Rhea:RHEA-COMP:15542, Rhea:RHEA-COMP:15546, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; Evidence={ECO:0000269|PubMed:10949293, ECO:0000269|PubMed:11283354};

Catalytic activity: Reaction=N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = H(+) + N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L- homocysteine; Xref=Rhea:RHEA:60284, Rhea:RHEA-COMP:15541, Rhea:RHEA- COMP:15542, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929, ChEBI:CHEBI:61976; Evidence={ECO:0000269|PubMed:11283354, ECO:0000269|PubMed:30051891};

Catalytic activity: Reaction=N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L- methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60288, Rhea:RHEA- COMP:15538, Rhea:RHEA-COMP:15541, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961, ChEBI:CHEBI:61976; Evidence={ECO:0000269|PubMed:30051891};

Catalytic activity: Reaction=L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6)- methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:51736, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13053, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; Evidence={ECO:0000269|PubMed:28143796};

Catalytic activity: Reaction=N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6),N(6)-dimethyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:54196, Rhea:RHEA-COMP:13053, Rhea:RHEA-COMP:13827, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929, ChEBI:CHEBI:61976; Evidence={ECO:0000269|PubMed:28143796};

Catalytic activity: Reaction=N(6),N(6)-dimethyl-L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + S-adenosyl-L- homocysteine; Xref=Rhea:RHEA:54200, Rhea:RHEA-COMP:13826, Rhea:RHEA- COMP:13827, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961, ChEBI:CHEBI:61976; Evidence={ECO:0000269|PubMed:28143796};

Activity regulation: An internal loop (autoregulatory loop) inhibits the catalytic activity of the enzyme by blocking the histone H3K9 substrate-binding pocket. Autocatalytic methylation of specific lysine residues in this loop promote a conformational switch that enhances the H3K9me activity of clr4. {ECO:0000269|PubMed:30051891}.

Subunit: Component of the Clr4 methyltransferase complex (ClrC) composed of at least clr4, rik1, pcu4, rbx1, raf1 and raf2. The cullin pcu4, rik1, raf1, raf2 and the ring-box protein rbx1 are components of an E3 ubiquitin ligase, whose activity is essential for heterochromatin assembly (PubMed:16024659, PubMed:16127433, PubMed:17114925, PubMed:12389037). Interacts directly with pcu4 (PubMed:16127433). Interacts with mlo3 (PubMed:21436456). {ECO:0000269|PubMed:12389037, ECO:0000269|PubMed:16024659, ECO:0000269|PubMed:16127433, ECO:0000269|PubMed:17114925, ECO:0000269|PubMed:21436456}.

Subcellular location: Nucleus {ECO:0000269|PubMed:16823372, ECO:0000269|PubMed:18345014}. Cytoplasm, cytoskeleton, microtubule organizing center, spindle pole body {ECO:0000269|PubMed:16823372}. Chromosome {ECO:0000269|PubMed:18345014, ECO:0000305|PubMed:16823372}.

Domain: The chromodomain serves to recognize and bind to H3K9me. {ECO:0000269|PubMed:18345014}.

Domain: In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.

Ptm: Autocatalytic methylation of specific lysine residues in an internal loop (autoregulatory loop) promote a conformational switch that enhances the H3K9me activity of clr4. {ECO:0000269|PubMed:30051891}.

Similarity: Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.

Annotations taken from UniProtKB at the EBI.


Organism:		Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
Taxonomy:		Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina; Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae; Schizosaccharomyces.



Function:		Histone methyltransferase which contributes to the establishment of heterochromatin by specifically methylating histone H3 to form H3K9me (PubMed:16024659, PubMed:8138176). Part of the Clr4 methyltransferase complex (ClrC). ClrC preferentially ubiquitylates H3K14 and ClrC-mediated H3 ubiquitination promotes clr4 methyltransferase activity (PubMed:31468675). Clr4 functions as a reader and writer of H3K9 methylation. It sets the H3K9me mark and afterwards this H3K9me mark is recognized by the chromodomains of clr4 and swi6/HP1, which then recruit additional clr4 leading to the methylation of neighboring nucleosomes (PubMed:11242054, PubMed:18345014, PubMed:21224386). H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting swi6/HP1 to methylated histones which leads to transcriptional silencing within centromeric heterochromatin, telomeres, ribosomal DNA repeats, and the silent mating-type region (PubMed:16024659, PubMed:8138176). Clr4 methyltransferase activity promotes the assembly of a tripartite complex composed of ClrC and complexes involved in siRNA generation (PubMed:20705239). Apart from H3K9, methylates also non-histone proteins such as mlo3 (PubMed:21436456, PubMed:28143796). Interacts with mlo3 to promote the processing of centromeric and antisense RNAs (PubMed:21436456). {ECO:0000269\|PubMed:11242054, ECO:0000269\|PubMed:16024659, ECO:0000269\|PubMed:18345014, ECO:0000269\|PubMed:20705239, ECO:0000269\|PubMed:21224386, ECO:0000269\|PubMed:21436456, ECO:0000269\|PubMed:28143796, ECO:0000269\|PubMed:31468675, ECO:0000269\|PubMed:8138176}.


Catalytic activity:		Reaction=L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + 3 S-adenosyl-L- homocysteine; Xref=Rhea:RHEA:60276, Rhea:RHEA-COMP:15538, Rhea:RHEA- COMP:15546, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.355; Evidence={ECO:0000269\|PubMed:11283354};
Catalytic activity:		Reaction=L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = H(+) + N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60280, Rhea:RHEA-COMP:15542, Rhea:RHEA-COMP:15546, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; Evidence={ECO:0000269\|PubMed:10949293, ECO:0000269\|PubMed:11283354};
Catalytic activity:		Reaction=N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = H(+) + N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L- homocysteine; Xref=Rhea:RHEA:60284, Rhea:RHEA-COMP:15541, Rhea:RHEA- COMP:15542, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929, ChEBI:CHEBI:61976; Evidence={ECO:0000269\|PubMed:11283354, ECO:0000269\|PubMed:30051891};
Catalytic activity:		Reaction=N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L- methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60288, Rhea:RHEA- COMP:15538, Rhea:RHEA-COMP:15541, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961, ChEBI:CHEBI:61976; Evidence={ECO:0000269\|PubMed:30051891};
Catalytic activity:		Reaction=L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6)- methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:51736, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13053, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; Evidence={ECO:0000269\|PubMed:28143796};
Catalytic activity:		Reaction=N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6),N(6)-dimethyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:54196, Rhea:RHEA-COMP:13053, Rhea:RHEA-COMP:13827, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929, ChEBI:CHEBI:61976; Evidence={ECO:0000269\|PubMed:28143796};
Catalytic activity:		Reaction=N(6),N(6)-dimethyl-L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + S-adenosyl-L- homocysteine; Xref=Rhea:RHEA:54200, Rhea:RHEA-COMP:13826, Rhea:RHEA- COMP:13827, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961, ChEBI:CHEBI:61976; Evidence={ECO:0000269\|PubMed:28143796};
Activity regulation:		An internal loop (autoregulatory loop) inhibits the catalytic activity of the enzyme by blocking the histone H3K9 substrate-binding pocket. Autocatalytic methylation of specific lysine residues in this loop promote a conformational switch that enhances the H3K9me activity of clr4. {ECO:0000269\|PubMed:30051891}.
Subunit:		Component of the Clr4 methyltransferase complex (ClrC) composed of at least clr4, rik1, pcu4, rbx1, raf1 and raf2. The cullin pcu4, rik1, raf1, raf2 and the ring-box protein rbx1 are components of an E3 ubiquitin ligase, whose activity is essential for heterochromatin assembly (PubMed:16024659, PubMed:16127433, PubMed:17114925, PubMed:12389037). Interacts directly with pcu4 (PubMed:16127433). Interacts with mlo3 (PubMed:21436456). {ECO:0000269\|PubMed:12389037, ECO:0000269\|PubMed:16024659, ECO:0000269\|PubMed:16127433, ECO:0000269\|PubMed:17114925, ECO:0000269\|PubMed:21436456}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:16823372, ECO:0000269\|PubMed:18345014}. Cytoplasm, cytoskeleton, microtubule organizing center, spindle pole body {ECO:0000269\|PubMed:16823372}. Chromosome {ECO:0000269\|PubMed:18345014, ECO:0000305\|PubMed:16823372}.
Domain:		The chromodomain serves to recognize and bind to H3K9me. {ECO:0000269\|PubMed:18345014}.
Domain:		In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.
Ptm:		Autocatalytic methylation of specific lysine residues in an internal loop (autoregulatory loop) promote a conformational switch that enhances the H3K9me activity of clr4. {ECO:0000269\|PubMed:30051891}.
Similarity:		Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00190}.