UniProt functional annotation for Q53H47



	UniProt functional annotation for Q53H47

UniProt code: Q53H47.

Organism: Homo sapiens (Human).

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

Function: Protein derived from the fusion of a methylase with the transposase of an Hsmar1 transposon that plays a role in DNA double- strand break repair, stalled replication fork restart and DNA integration. DNA-binding protein, it is indirectly recruited to sites of DNA damage through protein-protein interactions. Has also kept a sequence-specific DNA-binding activity recognizing the 19-mer core of the 5'-terminal inverted repeats (TIRs) of the Hsmar1 element and displays a DNA nicking and end joining activity (PubMed:16332963, PubMed:16672366, PubMed:17877369, PubMed:17403897, PubMed:18263876, PubMed:22231448, PubMed:24573677, PubMed:20521842). In parallel, has a histone methyltransferase activity and methylates 'Lys-4' and 'Lys-36' of histone H3. Specifically mediates dimethylation of H3 'Lys-36' at sites of DNA double-strand break and may recruit proteins required for efficient DSB repair through non-homologous end-joining (PubMed:16332963, PubMed:21187428, PubMed:22231448). Also regulates replication fork processing, promoting replication fork restart and regulating DNA decatenation through stimulation of the topoisomerase activity of TOP2A (PubMed:18790802, PubMed:20457750). {ECO:0000269|PubMed:16332963, ECO:0000269|PubMed:16672366, ECO:0000269|PubMed:17403897, ECO:0000269|PubMed:17877369, ECO:0000269|PubMed:18790802, ECO:0000269|PubMed:20457750, ECO:0000269|PubMed:20521842, ECO:0000269|PubMed:21187428, ECO:0000269|PubMed:22231448, ECO:0000269|PubMed:24573677, ECO:0000303|PubMed:18263876}.

Catalytic activity: Reaction=L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-methionine = 2 H(+) + N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] + 2 S-adenosyl-L- homocysteine; Xref=Rhea:RHEA:60308, Rhea:RHEA-COMP:9785, Rhea:RHEA- COMP:9787, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61976; EC=2.1.1.357; Evidence={ECO:0000269|PubMed:16332963};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Note=Binds 1 Mg(2+) ion per subunit.;

Subunit: Homodimer (PubMed:20521842). Interacts with PRPF19; required for SETMAR recruitment to damaged DNA sites (PubMed:18263876). Interacts with PCNA (PubMed:20457750). Interacts with TOP2A; stimulates TOP2A topoisomerase activity (PubMed:18790802, PubMed:20457750). May interact with RAD9A and/or RAD9B (PubMed:20457750). {ECO:0000269|PubMed:18263876, ECO:0000269|PubMed:18790802, ECO:0000269|PubMed:20457750, ECO:0000269|PubMed:20521842}.

Subcellular location: Nucleus {ECO:0000269|PubMed:18263876}. Chromosome {ECO:0000269|PubMed:18790802, ECO:0000269|PubMed:22231448}. Note=Recruited on damaged DNA at sites of double-strand breaks. {ECO:0000269|PubMed:18263876}.

Tissue specificity: Widely expressed, with highest expression in placenta and ovary and lowest expression in skeletal muscle. {ECO:0000269|PubMed:16332963}.

Domain: The mariner transposase Hsmar1 region mediates DNA-binding. It has retained some of the nucleases activity but has lost its transposase activity because the active site contains an Asn in position 610 instead of an Asp residue. {ECO:0000269|PubMed:17403897}.

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: Methylated. Methylation regulates activity in DNA decatenation. {ECO:0000269|PubMed:18790802}.

Ptm: Phosphorylated at Ser-508 by CHEK1 and dephosphorylated by protein phosphatase 2A/PP2A. Phosphorylation at Ser-508 is enhanced by DNA damage and promotes recruitment to damaged DNA. It stimulates DNA repair and impairs replication fork restart. {ECO:0000269|PubMed:22231448}.

Miscellaneous: The mariner transposase region in only present in primates and appeared 40-58 million years ago, after the insertion of a transposon downstream of a preexisting SET gene, followed by the de novo exonization of previously non-coding sequence and the creation of a new intron.

Similarity: In the N-terminal section; belongs to the class V-like SAM- binding methyltransferase superfamily. {ECO:0000305}.

Similarity: In the C-terminal section; belongs to the mariner transposase family. {ECO:0000305}.

Sequence caution: Sequence=AAH11635.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAY29570.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAD96454.1; 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:		Protein derived from the fusion of a methylase with the transposase of an Hsmar1 transposon that plays a role in DNA double- strand break repair, stalled replication fork restart and DNA integration. DNA-binding protein, it is indirectly recruited to sites of DNA damage through protein-protein interactions. Has also kept a sequence-specific DNA-binding activity recognizing the 19-mer core of the 5'-terminal inverted repeats (TIRs) of the Hsmar1 element and displays a DNA nicking and end joining activity (PubMed:16332963, PubMed:16672366, PubMed:17877369, PubMed:17403897, PubMed:18263876, PubMed:22231448, PubMed:24573677, PubMed:20521842). In parallel, has a histone methyltransferase activity and methylates 'Lys-4' and 'Lys-36' of histone H3. Specifically mediates dimethylation of H3 'Lys-36' at sites of DNA double-strand break and may recruit proteins required for efficient DSB repair through non-homologous end-joining (PubMed:16332963, PubMed:21187428, PubMed:22231448). Also regulates replication fork processing, promoting replication fork restart and regulating DNA decatenation through stimulation of the topoisomerase activity of TOP2A (PubMed:18790802, PubMed:20457750). {ECO:0000269\|PubMed:16332963, ECO:0000269\|PubMed:16672366, ECO:0000269\|PubMed:17403897, ECO:0000269\|PubMed:17877369, ECO:0000269\|PubMed:18790802, ECO:0000269\|PubMed:20457750, ECO:0000269\|PubMed:20521842, ECO:0000269\|PubMed:21187428, ECO:0000269\|PubMed:22231448, ECO:0000269\|PubMed:24573677, ECO:0000303\|PubMed:18263876}.


Catalytic activity:		Reaction=L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-methionine = 2 H(+) + N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] + 2 S-adenosyl-L- homocysteine; Xref=Rhea:RHEA:60308, Rhea:RHEA-COMP:9785, Rhea:RHEA- COMP:9787, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61976; EC=2.1.1.357; Evidence={ECO:0000269\|PubMed:16332963};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Note=Binds 1 Mg(2+) ion per subunit.;
Subunit:		Homodimer (PubMed:20521842). Interacts with PRPF19; required for SETMAR recruitment to damaged DNA sites (PubMed:18263876). Interacts with PCNA (PubMed:20457750). Interacts with TOP2A; stimulates TOP2A topoisomerase activity (PubMed:18790802, PubMed:20457750). May interact with RAD9A and/or RAD9B (PubMed:20457750). {ECO:0000269\|PubMed:18263876, ECO:0000269\|PubMed:18790802, ECO:0000269\|PubMed:20457750, ECO:0000269\|PubMed:20521842}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:18263876}. Chromosome {ECO:0000269\|PubMed:18790802, ECO:0000269\|PubMed:22231448}. Note=Recruited on damaged DNA at sites of double-strand breaks. {ECO:0000269\|PubMed:18263876}.
Tissue specificity:		Widely expressed, with highest expression in placenta and ovary and lowest expression in skeletal muscle. {ECO:0000269\|PubMed:16332963}.
Domain:		The mariner transposase Hsmar1 region mediates DNA-binding. It has retained some of the nucleases activity but has lost its transposase activity because the active site contains an Asn in position 610 instead of an Asp residue. {ECO:0000269\|PubMed:17403897}.
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:		Methylated. Methylation regulates activity in DNA decatenation. {ECO:0000269\|PubMed:18790802}.
Ptm:		Phosphorylated at Ser-508 by CHEK1 and dephosphorylated by protein phosphatase 2A/PP2A. Phosphorylation at Ser-508 is enhanced by DNA damage and promotes recruitment to damaged DNA. It stimulates DNA repair and impairs replication fork restart. {ECO:0000269\|PubMed:22231448}.
Miscellaneous:		The mariner transposase region in only present in primates and appeared 40-58 million years ago, after the insertion of a transposon downstream of a preexisting SET gene, followed by the de novo exonization of previously non-coding sequence and the creation of a new intron.
Similarity:		In the N-terminal section; belongs to the class V-like SAM- binding methyltransferase superfamily. {ECO:0000305}.
Similarity:		In the C-terminal section; belongs to the mariner transposase family. {ECO:0000305}.
Sequence caution:		Sequence=AAH11635.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAY29570.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAD96454.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};