UniProt functional annotation for Q96KQ7



	UniProt functional annotation for Q96KQ7

UniProt code: Q96KQ7.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself. {ECO:0000269|PubMed:11316813, ECO:0000269|PubMed:18438403, ECO:0000269|PubMed:20084102, ECO:0000269|PubMed:20118233, ECO:0000269|PubMed:22387026, ECO:0000269|PubMed:8457211}.

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:11316813, ECO:0000269|PubMed:20084102};

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:11316813, ECO:0000269|PubMed:20084102};

Subunit: Heterodimer; heterodimerizes with EHMT1/GLP (PubMed:16702210). Interacts with GFI1B and WIZ (PubMed:16688220, PubMed:16702210). Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EHMT1, RING1, RNF2, MBLR, L3MBTL2 and YAF2 (PubMed:12004135). Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2 (PubMed:21549307). Interacts with UHRF1 (PubMed:19056828). Interacts with CDYL (PubMed:19061646). Interacts with REST only in the presence of CDYL (PubMed:19061646). Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2 (PubMed:19061646). Interacts with PRDM9 and CDYL; interaction only takes place when PRDM9 is bound to hotspot DNA (By similarity). {ECO:0000250|UniProtKB:Q9Z148, ECO:0000269|PubMed:12004135, ECO:0000269|PubMed:16688220, ECO:0000269|PubMed:16702210, ECO:0000269|PubMed:19056828, ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:21549307}.

Subcellular location: Nucleus {ECO:0000269|PubMed:11316813}. Chromosome {ECO:0000269|PubMed:11316813}. Note=Associates with euchromatic regions. Does not associate with heterochromatin.

Tissue specificity: Expressed in all tissues examined, with high levels in fetal liver, thymus, lymph node, spleen and peripheral blood leukocytes and lower level in bone marrow. {ECO:0000269|PubMed:11707778}.

Domain: The SET domain mediates interaction with WIZ. {ECO:0000269|PubMed:18264113}.

Domain: The ANK repeats bind H3K9me1 and H3K9me2. {ECO:0000269|PubMed:18264113}.

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. {ECO:0000269|PubMed:18264113}.

Ptm: Methylated at Lys-185; automethylated. {ECO:0000269|PubMed:18438403}.

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

Sequence caution: Sequence=AAD21811.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAD21812.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAH02686.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH09351.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH18718.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH20970.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB63294.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=BAB63295.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAA49491.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself. {ECO:0000269\|PubMed:11316813, ECO:0000269\|PubMed:18438403, ECO:0000269\|PubMed:20084102, ECO:0000269\|PubMed:20118233, ECO:0000269\|PubMed:22387026, ECO:0000269\|PubMed:8457211}.


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:11316813, ECO:0000269\|PubMed:20084102};
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:11316813, ECO:0000269\|PubMed:20084102};
Subunit:		Heterodimer; heterodimerizes with EHMT1/GLP (PubMed:16702210). Interacts with GFI1B and WIZ (PubMed:16688220, PubMed:16702210). Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EHMT1, RING1, RNF2, MBLR, L3MBTL2 and YAF2 (PubMed:12004135). Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2 (PubMed:21549307). Interacts with UHRF1 (PubMed:19056828). Interacts with CDYL (PubMed:19061646). Interacts with REST only in the presence of CDYL (PubMed:19061646). Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2 (PubMed:19061646). Interacts with PRDM9 and CDYL; interaction only takes place when PRDM9 is bound to hotspot DNA (By similarity). {ECO:0000250\|UniProtKB:Q9Z148, ECO:0000269\|PubMed:12004135, ECO:0000269\|PubMed:16688220, ECO:0000269\|PubMed:16702210, ECO:0000269\|PubMed:19056828, ECO:0000269\|PubMed:19061646, ECO:0000269\|PubMed:21549307}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:11316813}. Chromosome {ECO:0000269\|PubMed:11316813}. Note=Associates with euchromatic regions. Does not associate with heterochromatin.
Tissue specificity:		Expressed in all tissues examined, with high levels in fetal liver, thymus, lymph node, spleen and peripheral blood leukocytes and lower level in bone marrow. {ECO:0000269\|PubMed:11707778}.
Domain:		The SET domain mediates interaction with WIZ. {ECO:0000269\|PubMed:18264113}.
Domain:		The ANK repeats bind H3K9me1 and H3K9me2. {ECO:0000269\|PubMed:18264113}.
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. {ECO:0000269\|PubMed:18264113}.
Ptm:		Methylated at Lys-185; automethylated. {ECO:0000269\|PubMed:18438403}.
Similarity:		Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00190}.
Sequence caution:		Sequence=AAD21811.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAD21812.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAH02686.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH09351.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAH18718.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH20970.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB63294.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=BAB63295.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAA49491.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};