SETMAR

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.

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.

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:17403897, PubMed:17877369, PubMed:18263876, PubMed:20521842, PubMed:22231448, PubMed:24573677). 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).

Methylated. Methylation regulates activity in DNA decatenation.

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.

In the N-terminal section; belongs to the class V-like SAM-binding methyltransferase superfamily.

In the C-terminal section; belongs to the mariner transposase family.

Widely expressed, with highest expression in placenta and ovary and lowest expression in skeletal muscle.

• Nucleus
• Chromosome
• Recruited on damaged DNA at sites of double-strand breaks.

Histone-lysine N-methyltransferase SETMAR, SET domain and mariner transposase fusion protein, Metnase, SETMAR

• entrezGene:6419
• omim:609834
• swissprot:Q53H47

Proteins

78034Da