Recombinant Human Histone-lysine N-methyltransferase SETD2 (SETD2), partial

1. Proteasome inhibition rescued SETD2 expression. PMID: 28663576
2. SETD2 is required to maintain high H3K79 di-methylation and MLL-AF9-binding to critical target genes, such as Hoxa9. PMID: 29777171
3. This study of patients with ccRCC, pooled analysis and multivariable modeling demonstrated that three recurrently mutated genes, BAP1, SETD2, and TP53, have statistically significant associations with poor clinical outcomes.important clinical confounders, mutations of TP53 and SETD2 were associated with decreased CSS and RFS, respectively. PMID: 28753773
4. SETD2 regulates tumor growth and chemosensitivity of osteosarcoma. Overexpression of SETD2 significantly inhibited osteosarcoma cell growth in vitro and in vivo. Moreover, SETD2 significantly enhanced cisplatin-induced apoptosis in osteosarcoma cells and inhibited cancer stem cell properties in OS cells. PMID: 29842882
5. Finally, mutations of H3G34 or H3P38 alleviate the inhibitory effects of H3K36M on H3K36 methylation, demonstrating that the stable interaction of H3K36M with SETD2 is critical for its inhibitory effects. PMID: 28256625
6. H3G34/R/V/D mutations impair the catalytic activity of SETD2 due to steric clashes that impede optimal SETD2-H3K36 interaction promoting genome instability and tumorigenesis by inhibiting mismatch repair activity. PMID: 30181289
7. SETD2 is a potential prognostic biomarker for overall survival and progression-free survival prediction in patients with metastatic renal cell carcinoma receiving targeted therapy PMID: 27288695
8. This study describes SETD2 inactivation as EATL-II molecular hallmark, supports EATL-I and -II being two distinct entities, and defines potential new targets for therapeutic intervention. PMID: 27600764
9. SETD2 and KDM5C mutations were associated with prolonged overall survival in patients with metastatic clear cell renal cell carcinoma PMID: 28408295
10. SETD2 expression was decreased in gastric cancer. Low-level expression of SETD2 in patients was significantly correlated with poor prognosis. Overexpression of SETD2 inhibited proliferation, migration, and invasion significantly in Gastric Cancer cell lines. PMID: 29522714
11. The fusion transcript codes for a protein in which the last 114 amino acids of SETD2, i.e., the entire Set2 Rpb1 interacting (SRI) domain of SETD2, are replaced by 30 amino acids encoded by the NF1 sequence. PMID: 28498454
12. Our work defines SETD2 as a tumor suppressor gene in Hepatosplenic T-cell lymphoma (HSTL)and implicates genes including INO80 and PIK3CD in the disease PMID: 28122867
13. The findings, specifically frequent mutations of STAT5B, PIK3CD, and the histone methyltransferase SETD2, may help guide translational efforts to target hepatosplenic T-cell lymphoma PMID: 28373165
14. SETD2 Mutation is associated with Clear Cell Renal Cell Carcinomas. PMID: 28754676
15. SETD2 downregulation affects the alternative splicing of a subset of genes implicated in intestinal tumorigenesis PMID: 28825595
16. frequently mutated in enteropathy-associated T cell lymphoma and plays a role in T cell development PMID: 28424246
17. SETD2 aberration as a recurrent, early loss-of-function event in CLL pathobiology linked to aggressive disease PMID: 27282254
18. Setd2 as a potent tumor suppressor in lung adenocarcinoma. PMID: 28202515
19. This study reports a new role for SETD2 in promoting IFNalpha-induced antiviral immune response by directly methylating STAT1 on lysine 525 and catalyzing H3K36me3 on the promoters of some IFN-stimulated genes (ISGs such as ISG15) to activate gene transcription. Thus, SETD2 enhances host antiviral immunity by strengthening IFNalpha signaling both post-translationally and epigenetically. PMID: 28753426
20. SETD2 is a novel GIST tumour suppressor gene associated with disease progression. PMID: 26338826
21. Results identified new role for SETD2 in the methylation of K40 of alpha-tubulin. Loss of SETD2 abolishes methylation of K40 of alpha-tubulin and results in a dysfunctional mitotic spindle and abnormalities in cytokinesis. Thus, SETD2 links chromatin and cytoskeleton homeostasis through its methyltransferase activity. PMID: 27528705
22. Data suggest post-translational modifications of histones, trimethylation of lysine 36 in H3 (H3K36me3) and acetylation of lysine 16 in H4 (H4K16ac), have roles in DNA damage repair; H3K36me3 stimulates H4K16ac upon DNA double-strand break; SETD2, LEDGF, and KAT5 are required for these epigenetic changes. (SETD2 = SET domain containing 2; LEDGF = lens epithelium-derived growth factor; KAT5 = lysine acetyltransferase 5) PMID: 28546430
23. SETD2 gene deletion is associated with chordoma. PMID: 27072194
24. SPOP-containing complex regulates SETD2 stability and H3K36me3-coupled alternative splicing. PMID: 27614073
25. one of these mutations (R2510H), located in the Set2 Rpb1 interaction domain, did not result in an observable defect in SETD2 enzymatic function, a second mutation in the catalytic domain of this enzyme (R1625C) resulted in a complete loss of histone H3 Lys-36 trimethylation (H3K36me3). PMID: 27528607
26. functional loss of SETD2 enables renal primary tubular epithelial cells to bypass the senescence barrier by maintaining CDKN2A-E2F signaling, facilitating a malignant transformation toward Clear Cell Renal Cell Carcinoma. PMID: 27292023
27. Mutation in SETD2 gene is associated with renal cell carcinoma. PMID: 26646321
28. Data identify SETD2 as a dual-function methyltransferase for both chromatin and the cytoskeleton and show a requirement for methylation in maintenance of genomic stability and the integrity of both the tubulin and histone codes. PMID: 27518565
29. This study provides evidence for HOTAIR to promote tumorigenesis via downregulating SETD2 in liver cancer stem cells. PMID: 26172293
30. Use bioinformatic tools to predict the molecular effects of all mutations lying in SETD2 genes. PMID: 26452128
31. This study provide the evidence SETD2 mutation releate to Autism Spectrum Disorder. PMID: 26637798
32. Data show that SETD2 mutations are not associated with microsatellite instability in renal cancer and suggest a role for SETD2 in maintaining genome integrity through nucleosome stabilization, DNA repair and suppression of replication stress. PMID: 25728682
33. Findings extend the knowledge about the regulation of SETD2 at the posttranscriptional level by miRNA and regulatory mechanism downstream of SETD2 in ccRCC. PMID: 25714014
34. loss of SETD2 may afford an alternative mechanism for the inactivation of the p53-mediated checkpoint without the need for additional genetic mutations in TP53. PMID: 24843002
35. Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia. PMID: 24662245
36. miRNA network regulates SETD2 in in colorectal metastasis tissues. PMID: 26069251
37. Both ASH1L and SETD2 are H3K36 specific methyltransferases but only SETD2 can trimethylate this mark. PMID: 26002201
38. found that SETD2 mutation also mediated MMR via AKT-induced PMS2 decrease and co-loss of MLH1 loss in renal clear cell carcinoma PMID: 25528216
39. HYPB interacts with the proline-rich region of HTT protein. PMID: 24412394
40. association of SETD2 mutations with multiple major chromosomal translocations implies a common mechanism in various subtypes of leukemia with SETD2 mutations PMID: 25077743
41. Data establish a presynaptic role for SETD2 methyltransferase in HR; it facilitates the recruitment of C-terminal binding protein interacting protein and promotes DSB resection, allowing Replication Protein A (RPA) and RAD51 binding to DNA damage sites. PMID: 24931610
42. Identified two heterozygous mutations in the SETD2 gene in two patients with 'Sotos-like' syndrome. PMID: 24852293
43. Results implicate SETD2 as a tumor suppressor gene and demonstrate that loss-of-function SETD2 mutations can facilitate the initiation and maintenance of leukemias with chromosomal translocations through a global reduction of H3K36me3. PMID: 24706662
44. These results directly link mutations in SETD2 to chromatin accessibility changes and RNA processing defects in cancer PMID: 24158655
45. loss-of-function point mutations in SETD2 were recurrent (6.2%) in 241 patients with acute leukemia and were associated with multiple major chromosomal aberrations PMID: 24509477
46. Mutation frequencies among CT images of clear cell RCCs were as follows: SETD2, 7.3% (17 of 233). PMID: 24029645
47. PBRM1, KDM6A, SETD2 and BAP1 were unmethylated in all tumor and normal specimens. PMID: 23644518
48. BAP1 and SETD2 mutations (6%-12%) are associated with worse cancer-specific survival , suggesting their roles in disease progression. PMID: 23620406
49. SETD3 exhibits histone methyltransferases activity on nucleosomal histone 3 in a SET-domain dependent manner. We propose that this newly identified Setd3 gene may play an important role in carcinogenesis. PMID: 23065515
50. SETD2 mutations were found to be specific to high-grade gliomas affecting 15% of pediatric tumors(11/73) and 8% of adult high-grade gliomas (5/65), while no SETD2 mutations were identified in low-grade diffuse gliomas. PMID: 23417712

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HGNC: 18420

OMIM: 144700

KEGG: hsa:29072

STRING: 9606.ENSP00000386759

UniGene: Hs.517941