| Tbio | Histone-lysine N-methyltransferase SETMAR |
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).
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. [provided by RefSeq, Jan 2013]
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. [provided by RefSeq, Jan 2013]
Comments
| Disease | Target Count | P-value |
|---|---|---|
| ovarian cancer | 8492 | 1.06317113462096E-9 |
| osteosarcoma | 7933 | 1.20737625966349E-6 |
| malignant mesothelioma | 3163 | 3.08035567682522E-6 |
| group 4 medulloblastoma | 1875 | 3.77553322933865E-6 |
| medulloblastoma, large-cell | 6234 | 5.97338360411156E-6 |
| inflammatory breast cancer | 404 | 1.21136754444031E-5 |
| posterior fossa group B ependymoma | 1530 | 1.48737312611115E-5 |
| atypical teratoid / rhabdoid tumor | 4369 | 5.48126585852597E-4 |
| psoriasis | 6685 | 0.00110002071977537 |
| intraductal papillary-mucinous neoplasm (IPMN) | 3289 | 0.00177484124914862 |
| adult high grade glioma | 2148 | 0.00216420572250187 |
| Disease | log2 FC | p |
|---|---|---|
| malignant mesothelioma | 1.300 | 0.000 |
| psoriasis | -1.100 | 0.001 |
| osteosarcoma | 2.019 | 0.000 |
| group 4 medulloblastoma | 1.500 | 0.000 |
| atypical teratoid / rhabdoid tumor | 1.100 | 0.001 |
| medulloblastoma, large-cell | 1.600 | 0.000 |
| intraductal papillary-mucinous neoplasm ... | -1.300 | 0.002 |
| adult high grade glioma | 1.200 | 0.002 |
| posterior fossa group B ependymoma | 1.200 | 0.000 |
| inflammatory breast cancer | -1.100 | 0.000 |
| ovarian cancer | 1.400 | 0.000 |
| PMID | Text |
|---|---|
| 26437079 | The SET domain is needed for the 5' end of ss-overhang cleavage with fork and non-fork DNA without affecting the Metnase-DNA interaction. This domain has a positive role in restart of replication fork and the 5' end of ss-overhang cleavage. |
| 25795785 | methylation of snRNP70 by SETMAR regulates constitutive and/or alternative splicing |
| 25333365 | Metnase may possess an important role in DNA repair, topoisomerase II function, and the maintenance of stemness during colon cancer development. |
| 24655462 | 293 T transfected with Metnase revealed a large number of rescued plasmids. |
| 24607956 | found known and novel SETMAR splice variants to be significantly increased in acute myeloid leukemia |
| 24573677 | a single mutation DDN(610) --> DDD(610), which restores the ancestral catalytic site, results in loss of function in Metnase |
| 22231448 | phosphorylation of Metnase S495 differentiates between these two functions, enhancing DSB repair and repressing replication fork restart. |
| 21491884 | a role for Metnase's endonuclease activity in promoting the joining of noncompatible ends |
| 21187428 | DNA repair protein Metnase (also SETMAR), which has a SET histone methylase domain, localized to an induced DSB and directly mediated the formation of H3K36me2 near the induced DSB |
| 21124928 | Data show that DBN1, SETMAR and HIG2 are direct transcriptional targets of the SOX11 protein. |
| More... |
MFAEAAKTTRPCGMAEFKEKPEAPTEQLDVACGQENLPVGAWPPGAAPAPFQYTPDHVVGPGADIDPTQI 1 - 70 TFPGCICVKTPCLPGTCSCLRHGENYDDNSCLRDIGSGGKYAEPVFECNVLCRCSDHCRNRVVQKGLQFH 71 - 140 FQVFKTHKKGWGLRTLEFIPKGRFVCEYAGEVLGFSEVQRRIHLQTKSDSNYIIAIREHVYNGQVMETFV 141 - 210 DPTYIGNIGRFLNHSCEPNLLMIPVRIDSMVPKLALFAAKDIVPEEELSYDYSGRYLNLTVSEDKERLDH 211 - 280 GKLRKPCYCGAKSCTAFLPFDSSLYCPVEKSNISCGNEKEPSMCGSAPSVFPSCKRLTLETMKMMLDKKQ 281 - 350 IRAIFLFEFKMGRKAAETTRNINNAFGPGTANERTVQWWFKKFCKGDESLEDEERSGRPSEVDNDQLRAI 351 - 420 IEADPLTTTREVAEELNVNHSTVVRHLKQIGKVKKLDKWVPHELTENQKNRRFEVSSSLILRNHNEPFLD 421 - 490 RIVTCDEKWILYDNRRRSAQWLDQEEAPKHFPKPILHPKKVMVTIWWSAAGLIHYSFLNPGETITSEKYA 491 - 560 QEIDEMNQKLQRLQLALVNRKGPILLHDNARPHVAQPTLQKLNELGYEVLPHPPYSPDLLPTNYHVFKHL 561 - 630 NNFLQGKRFHNQQDAENAFQEFVESQSTDFYATGINQLISRWQKCVDCNGSYFD 631 - 684 //
| PMID | Year | Title |
|---|---|---|
| 26437079 | 2015 | The SET Domain Is Essential for Metnase Functions in Replication Restart and the 5' End of SS-Overhang Cleavage. |
| 25795785 | 2015 | A Proteomic Strategy Identifies Lysine Methylation of Splicing Factor snRNP70 by the SETMAR Enzyme. |
| 25333365 | 2014 | Potential role for the Metnase transposase fusion gene in colon cancer through the regulation of key genes. |
| 24655462 | 2014 | Fidelity of end joining in mammalian episomes and the impact of Metnase on joint processing. |
| 24607956 | 2014 | Delineation of known and new transcript variants of the SETMAR (Metnase) gene and the expression profile in hematologic neoplasms. |
| 24573677 | 2014 | The DDN catalytic motif is required for Metnase functions in non-homologous end joining (NHEJ) repair and replication restart. |
| 24024966 | 2013 | Genome-wide association study of chronic periodontitis in a general German population. |
| 23186163 | 2013 | Toward a comprehensive characterization of a human cancer cell phosphoproteome. |
| 22231448 | 2012 | Chk1 phosphorylation of Metnase enhances DNA repair but inhibits replication fork restart. |
| 21491884 | 2011 | Biochemical characterization of metnase's endonuclease activity and its role in NHEJ repair. |
| More... |
