SETMAR

This gene encodes a fusion protein that contains an N-terminal histone-lysine N-methyltransferase domain and a C-terminal mariner transposase domain. The encoded protein binds DNA and functions in DNA repair activities including non-homologous end joining and double strand break repair. The SET domain portion of this protein specifically methylates histone H3 lysines 4 and 36. This gene exists as a fusion gene only in anthropoid primates, other organisms lack mariner transposase domain. Alternate splicing results in multiple transcript variants.

SET Domain And Mariner Transposase Fusion Gene

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).

Biological Process cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process chromatin organizationIEA:UniProtKB-KW
Biological Process DNA catabolic process, endonucleolyticManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process DNA double-strand break processingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process DNA integrationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process double-strand break repair via nonhomologous end joiningManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process histone H3-K36 dimethylationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process histone H3-K36 methylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process histone H3-K4 methylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process mitotic DNA integrity checkpoint signalingManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of chromosome organizationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process nucleic acid phosphodiester bond hydrolysisManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of DNA topoisomerase (ATP-hydrolyzing) activityManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of double-strand break repair via nonhomologous end joiningManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process replication fork processingManual Assertion Based On ExperimentIMP:UniProtKB

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

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.