From Wikipedia, the free encyclopedia
Jump to: navigation, search
Available structures
PDB Ortholog search: PDBe RCSB
Aliases SMYD3, KMT3E, ZMYND1, ZNFN3A1, bA74P14.1, SET and MYND domain containing 3
External IDs MGI: 1916976 HomoloGene: 41491 GeneCards: SMYD3
Genetically Related Diseases
RNA expression pattern
PBB GE SMYD3 218788 s at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 1: 245.75 – 246.51 Mb Chr 1: 178.95 – 179.52 Mb
PubMed search [2] [3]
View/Edit Human View/Edit Mouse

SET and MYND domain-containing protein 3 is a protein that in humans is encoded by the SMYD3 gene.[4]


SMYD3 is a histone methyltransferase that plays a role in transcriptional regulation as a member of an RNA polymerase complex.[4]

Model organisms[edit]

Model organisms have been used in the study of SMYD3 function. A conditional knockout mouse line, called Smyd3tm2a(KOMP)Wtsi[9][10] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[11][12][13]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[7][14] Twenty three tests were carried out on homozygous mutant adult mice, however no significant abnormalities were observed.[7]


SMYD3 has been shown to interact with Heat shock protein 90kDa alpha (cytosolic), member A1[15] and POLR2A.[15]

SMYD3 trimethylates a lysine residue on MAP3K2, which causes crosstalk into the MAP kinase signaling pathway in Ras-driven cancers.[16]


  1. ^ "Diseases that are genetically associated with SMYD3 view/edit references on wikidata". 
  2. ^ "Human PubMed Reference:". 
  3. ^ "Mouse PubMed Reference:". 
  4. ^ a b "Entrez Gene: SMYD3 SET and MYND domain containing 3". 
  5. ^ "Salmonella infection data for Smyd3". Wellcome Trust Sanger Institute. 
  6. ^ "Citrobacter infection data for Smyd3". Wellcome Trust Sanger Institute. 
  7. ^ a b c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. 
  8. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  9. ^ "International Knockout Mouse Consortium". 
  10. ^ "Mouse Genome Informatics". 
  11. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410Freely accessible. PMID 21677750. 
  12. ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  13. ^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  14. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837Freely accessible. PMID 21722353. 
  15. ^ a b Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, Yagyu R, Nakamura Y (Aug 2004). "SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells". Nature Cell Biology. 6 (8): 731–40. doi:10.1038/ncb1151. PMID 15235609. 
  16. ^ Mazur PK, Reynoird N, Khatri P, Jansen PW, Wilkinson AW, Liu S, Barbash O, Van Aller GS, Huddleston M, Dhanak D, Tummino PJ, Kruger RG, Garcia BA, Butte AJ, Vermeulen M, Sage J, Gozani O (Jun 2014). "SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer". Nature. 510 (7504): 283–7. doi:10.1038/nature13320. PMID 24847881. 

Further reading[edit]

  • Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM (Jan 2004). "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region". Genomics. 83 (1): 153–67. doi:10.1016/S0888-7543(03)00235-0. PMID 14667819. 
  • Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, Yagyu R, Nakamura Y (Aug 2004). "SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells". Nature Cell Biology. 6 (8): 731–40. doi:10.1038/ncb1151. PMID 15235609. 
  • Zhou Z, Ren X, Huang X, Lu L, Xu M, Yin L, Li J, Sha J (2006). "SMYD3-NY, a novel SMYD3 mRNA transcript variant, may have a role in human spermatogenesis". Annals of Clinical and Laboratory Science. 35 (3): 270–7. PMID 16081583. 
  • Tsuge M, Hamamoto R, Silva FP, Ohnishi Y, Chayama K, Kamatani N, Furukawa Y, Nakamura Y (Oct 2005). "A variable number of tandem repeats polymorphism in an E2F-1 binding element in the 5' flanking region of SMYD3 is a risk factor for human cancers". Nature Genetics. 37 (10): 1104–7. doi:10.1038/ng1638. PMID 16155568. 
  • Hamamoto R, Silva FP, Tsuge M, Nishidate T, Katagiri T, Nakamura Y, Furukawa Y (Feb 2006). "Enhanced SMYD3 expression is essential for the growth of breast cancer cells". Cancer Science. 97 (2): 113–8. doi:10.1111/j.1349-7006.2006.00146.x. PMID 16441421. 
  • Wang XQ, Miao X, Cai Q, Garcia-Barcelo MM, Fan ST (Mar 2007). "SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population". Experimental Oncology. 29 (1): 71–3. PMID 17431393.