SMYD3

SET and MYND domain containing 3
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3MEK​, 3OXF​, 3OXG​, 3OXL​, 3PDN​, 3QWP​, 3RU0​
Identifiers
Symbols	SMYD3 ; KMT3E; ZMYND1; ZNFN3A1; bA74P14.1
External IDs	OMIM: 608783 MGI: 1916976 HomoloGene: 41491 GeneCards: SMYD3 Gene
EC number	2.1.1.43
Gene ontology Molecular function • histone-lysine N-methyltransferase activity • metal ion binding Cellular component • nucleoplasm • cytoplasm Biological process • chromatin organization • histone lysine methylation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	64754	69726
Ensembl	ENSG00000185420	ENSMUSG00000055067
UniProt	Q9H7B4	Q9CWR2
RefSeq (mRNA)	NM_001167740	NM_027188
RefSeq (protein)	NP_001161212	NP_081464
Location (UCSC)	Chr 1: 245.75 – 246.51 Mb	Chr 1: 178.95 – 179.52 Mb
PubMed search

SET and MYND domain-containing protein 3 is a protein that in humans is encoded by the SMYD3 gene.^[1]

Function

SMYD3 is a histone methyltransferase that plays a role in transcriptional regulation as a member of an RNA polymerase complex.^[1]

Model organisms

Smyd3 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Brain histopathology	Normal
Salmonella infection	Normal[2]
Citrobacter infection	Normal[3]
All tests and analysis from[4][5]

Model organisms have been used in the study of SMYD3 function. A conditional knockout mouse line, called Smyd3^{tm2a(KOMP)Wtsi[6][7]} 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.^[8][9][10]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[4][11] Twenty three tests were carried out on homozygous mutant adult mice, however no significant abnormalities were observed.^[4]

Interactions

SMYD3 has been shown to interact with Heat shock protein 90kDa alpha (cytosolic), member A1^[12] and POLR2A.^[12]

SMYD3 trimethylates a lysine residue on MAP3K2, which causes crosstalk into the MAP kinase signaling pathway in Ras-driven cancers.^[13]

References

1. "Entrez Gene: SMYD3 SET and MYND domain containing 3".
2. "Salmonella infection data for Smyd3". Wellcome Trust Sanger Institute.
3. "Citrobacter infection data for Smyd3". Wellcome Trust Sanger Institute.
4. 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.
5. Mouse Resources Portal, Wellcome Trust Sanger Institute.
6. "International Knockout Mouse Consortium".
7. "Mouse Genome Informatics".
8. 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 3572410. PMID 21677750.
9. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
10. 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.
11. 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 3218837. PMID 21722353.
12. 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.
13. 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

• 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.