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Protein SETD2 PDB 2a7o.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesSETD2, HBP231, HIF-1, HIP-1, HYPB, KMT3A, SET2, p231HBP, HSPC069, LLS, SET domain containing 2
External IDsMGI: 1918177 HomoloGene: 56493 GeneCards: SETD2
Gene location (Human)
Chromosome 3 (human)
Chr.Chromosome 3 (human)[1]
Chromosome 3 (human)
Genomic location for SETD2
Genomic location for SETD2
Band3p21.31Start47,016,429 bp[1]
End47,163,967 bp[1]
RNA expression pattern
PBB GE SETD2 212493 s at fs.png

PBB GE SETD2 220946 s at fs.png

PBB GE SETD2 215038 s at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



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

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


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[edit]

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]


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]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000181555 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000044791 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  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.
  7. ^ a b c "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[edit]