SETD2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSETD2, HBP231, HIF-1, HIP-1, HYPB, KMT3A, SET2, p231HBP, HSPC069, LLS, SET domain containing 2
External IDsOMIM: 612778 MGI: 1918177 HomoloGene: 56493 GeneCards: SETD2
Orthologs
SpeciesHumanMouse
Entrez

29072

235626

Ensembl

ENSG00000181555

ENSMUSG00000044791

UniProt

Q9BYW2

E9Q5F9

RefSeq (mRNA)

NM_012271
NM_014159
NM_001349370

NM_001081340

RefSeq (protein)

NP_054878
NP_001336299

NP_001074809

Location (UCSC)Chr 3: 47.02 – 47.16 MbChr 9: 110.53 – 110.62 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

SET domain containing 2 is an enzyme that in humans is encoded by the SETD2 gene.[5][6][7]

Function

SETD2 protein is a histone methyltransferase that is specific for lysine-36 of histone H3, and methylation of this residue is associated with active chromatin. This protein also contains a novel transcriptional activation domain and has been found associated with hyperphosphorylated RNA polymerase II.[7]

The trimethylation of lysine-36 of histone H3 (H3K36me3) is required in human cells for homologous recombinational repair and genome stability.[8] Depletion of SETD2 increases the frequency of deletion mutations that arise by the alternative DNA repair process of microhomology-mediated end joining.

Clinical significance

The SETD2 gene is located on the short arm of chromosome 3 and has been shown to play a tumour suppressor role in human cancer.[9]

Interactions

SETD2 has been shown to interact with Huntingtin.[10] Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. SETD2 belongs to a class of huntingtin interacting proteins characterized by WW motifs.[7]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000181555 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000044791 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Sun XJ, Wei J, Wu XY, Hu M, Wang L, Wang HH, Zhang QH, Chen SJ, Huang QH, Chen Z (Oct 2005). "Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase". J Biol Chem. 280 (42): 35261–71. doi:10.1074/jbc.M504012200. PMID 16118227.
  6. Rega S, Stiewe T, Chang DI, Pollmeier B, Esche H, Bardenheuer W, Marquitan G, Putzer BM (Jul 2001). "Identification of the full-length huntingtin- interacting protein p231HBP/HYPB as a DNA-binding factor". Mol Cell Neurosci. 18 (1): 68–79. doi:10.1006/mcne.2001.1004. PMID 11461154. S2CID 31658986.
  7. 1 2 3 "Entrez Gene: SETD2 SET domain containing 2".
  8. Pfister SX, Ahrabi S, Zalmas LP, Sarkar S, Aymard F, Bachrati CZ, Helleday T, Legube G, La Thangue NB, Porter AC, Humphrey TC (June 2014). "SETD2-dependent histone H3K36 trimethylation is required for homologous recombination repair and genome stability". Cell Rep. 7 (6): 2006–18. doi:10.1016/j.celrep.2014.05.026. PMC 4074340. PMID 24931610.
  9. Al Sarakbi W, Sasi W, Jiang WG, Roberts T, Newbold RF, Mokbel K (2009). "The mRNA expression of SETD2 in human breast cancer: correlation with clinico-pathological parameters". BMC Cancer. 9: 290. doi:10.1186/1471-2407-9-290. PMC 3087337. PMID 19698110.
  10. Faber PW, Barnes GT, Srinidhi J, Chen J, Gusella JF, MacDonald ME (September 1998). "Huntingtin interacts with a family of WW domain proteins". Hum. Mol. Genet. 7 (9): 1463–74. doi:10.1093/hmg/7.9.1463. PMID 9700202.

Further reading


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