SETD2

SET domain containing 2 is an enzyme that in humans is encoded by the SETD2 gene.

SETD2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2A7O, 2MDC, 2MDI, 2MDJ, 4FMU, 4H12
Identifiers
Aliases	SETD2, HBP231, HIF-1, HIP-1, HYPB, KMT3A, SET2, p231HBP, HSPC069, LLS, SET domain containing 2
External IDs	OMIM: 612778; MGI: 1918177; HomoloGene: 56493; GeneCards: SETD2; OMA:SETD2 - orthologs
Gene location (Human) Chr. Chromosome 3 (human) Band 3p21.31 Start 47,016,429 bp End 47,163,967 bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9|9 F2 Start 110,532,597 bp End 110,618,633 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tendon of biceps brachii endothelial cell epithelium of colon Achilles tendon ventricular zone sural nerve pancreatic ductal cell ganglionic eminence internal globus pallidus tonsil Top expressed in hand genital tubercle tail of embryo ventricular zone morula neural layer of retina granulocyte mesenteric lymph nodes thymus epiblast More reference expression data BioGPS More reference expression data
Gene ontology Molecular function methyltransferase activity transferase activity protein binding histone-lysine N-methyltransferase activity protein-lysine N-methyltransferase activity alpha-tubulin binding histone methyltransferase activity (H3-K36 specific) metal ion binding Cellular component nucleoplasm nucleus chromosome Biological process regulation of transcription, DNA-templated histone H3-K36 dimethylation regulation of mRNA export from nucleus embryonic organ development stem cell development embryonic placenta morphogenesis transcription elongation from RNA polymerase II promoter coronary vasculature morphogenesis cell migration involved in vasculogenesis morphogenesis of a branching structure transcription, DNA-templated mesoderm morphogenesis vasculogenesis histone H3-K36 methylation methylation neural tube closure nucleosome organization angiogenesis pericardium development regulation of gene expression histone H3-K36 trimethylation embryonic cranial skeleton morphogenesis DNA mismatch repair histone lysine methylation forebrain development regulation of double-strand break repair via homologous recombination peptidyl-lysine trimethylation peptidyl-lysine monomethylation regulation of cytokinesis positive regulation of interferon-alpha production response to type I interferon endodermal cell differentiation stem cell differentiation microtubule cytoskeleton organization involved in mitosis regulation of protein localization to chromatin immune system process DNA repair cellular response to DNA damage stimulus multicellular organism development cell differentiation innate immune response defense response to virus chromatin organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 9: 110.53 – 110.62 Mb PubMed search
Wikidata
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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.

The trimethylation of lysine-36 of histone H3 (H3K36me3) is required in human cells for homologous recombinational repair and genome stability. 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.

Interactions

SETD2 has been shown to interact with Huntingtin. 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.

Further reading

• Faber PW, Barnes GT, Srinidhi J, et al. (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.
• Passani LA, Bedford MT, Faber PW, et al. (2000). "Huntingtin's WW domain partners in Huntington's disease post-mortem brain fulfill genetic criteria for direct involvement in Huntington's disease pathogenesis". Hum. Mol. Genet. 9 (14): 2175–82. doi:10.1093/hmg/9.14.2175. PMID 10958656.
• Zhang QH, Ye M, Wu XY, et al. (2001). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
• Nagase T, Kikuno R, Hattori A, et al. (2001). "Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (6): 347–55. doi:10.1093/dnares/7.6.347. PMID 11214970.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Li M, Phatnani HP, Guan Z, et al. (2006). "Solution structure of the Set2-Rpb1 interacting domain of human Set2 and its interaction with the hyperphosphorylated C-terminal domain of Rpb1". Proc. Natl. Acad. Sci. U.S.A. 102 (49): 17636–41. doi:10.1073/pnas.0506350102. PMC 1308900. PMID 16314571.
• Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685.
• Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.