SMYD2

SMYD2
Identifiers
Aliases	SMYD2, HSKM-B, KMT3C, ZMYND14, SET and MYND domain containing 2
External IDs	OMIM: 610663; MGI: 1915889; GeneCards: SMYD2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3RIB, 3S7B, 3S7D, 3S7F, 3S7J, 3TG4, 3TG5, 4O6F, 4WUY, 4YND, 5ARF, 5ARG
Enzyme activity
Gene location (Human)
Chr.	Chromosome 1 (human)
End	214,337,131 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	189,654,560 bp
RNA expression pattern
	Top expressed in
	myocardium of left ventricle; ; right ventricle; ; apex of heart; ; epithelium of bronchus; ; bronchial epithelial cell; ; vastus lateralis muscle; ; glutes; ; mucosa of paranasal sinus; ; thoracic diaphragm; ; skeletal muscle tissue;
	Top expressed in
	gastrocnemius muscle; ; vastus lateralis muscle; ; medial head of gastrocnemius muscle; ; endocardial cushion; ; triceps brachii muscle; ; tibialis anterior muscle; ; facial motor nucleus; ; atrioventricular valve; ; muscle of thigh; ; anterior horn of spinal cord;
	More reference expression data
	n/a
Gene ontology
Molecular function	methyltransferase activity; transferase activity; RNA polymerase II complex binding; p53 binding; metal ion binding; protein-lysine N-methyltransferase activity; protein binding; histone methyltransferase activity (H3-K36 specific); lysine N-methyltransferase activity; histone-lysine N-methyltransferase activity;
Cellular component	cytosol; nucleoplasm; nucleus; cytoplasm;
Biological process	regulation of DNA damage response, signal transduction by p53 class mediator; regulation of transcription, DNA-templated; negative regulation of transcription by RNA polymerase II; peptidyl-lysine monomethylation; transcription, DNA-templated; histone H3-K36 methylation; development of the heart; methylation; peptidyl-lysine dimethylation; histone methylation; negative regulation of cell population proliferation; histone lysine methylation; regulation of signal transduction by p53 class mediator; chromatin organization;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	56950
	226830
	ENSG00000143499
	ENSMUSG00000026603
	Q9NRG4
	Q8R5A0
	NM_020197
	NM_026796
	NP_064582
	NP_081072
	Wikidata
View/Edit Human	View/Edit Mouse

SET and MYND domain containing 2 is a protein that in humans is encoded by the SMYD2 gene.

Function

SMYD2 belongs to the SET and MYND domain-containing (SMYD) family of protein lysine methyltransferases, which methylate lysine residues in both histone and non-histone substrates.

This enzyme methylates histone H3 at lysine 4 and lysine 36. In addition, it methylates a broad range of non-histone proteins, including the tumor suppressors p53 and Rb, the molecular chaperone Hsp90, estrogen receptor α, and PARP1. This methylation affects the stability and function of target proteins and hence is able to regulate a significant number of cellular processes including apoptosis and cell cycle progression.

Clinical significance

Because SMYD2 methylation of p53 and Rb interferes with their tumor suppressor function, over expression of SMYD2 has been associated with worse outcomes in numerous types of cancer, including esophageal squamous cell carcinoma, breast, gastric, hepatocellular, and pancreatic ductal adenocarcinoma. These cancer associations have led to the development of small-molecule inhibitors of SMYD2 that suppress the proliferation of cancer cell lines.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000143499 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026603 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 3 Zheng Q, Zhang W, Rao GW (August 2022). "Protein Lysine Methyltransferase SMYD2: A Promising Small Molecule Target for Cancer Therapy". Journal of Medicinal Chemistry. 65 (15): 10119–10132. doi:10.1021/acs.jmedchem.2c00325. PMID 35914250.
↑ Yi X, Jiang XJ, Fang ZM (August 2019). "Histone methyltransferase SMYD2: ubiquitous regulator of disease". Clinical Epigenetics. 11 (1) 112. doi:10.1186/s13148-019-0711-4. PMC 6670139. PMID 31370883.
↑ Spellmon N, Holcomb J, Trescott L, Sirinupong N, Yang Z (January 2015). "Structure and function of SET and MYND domain-containing proteins". International Journal of Molecular Sciences. 16 (1): 1406–1428. doi:10.3390/ijms16011406. PMC 4307310. PMID 25580534.

Rubio-Tomás T (November 2021). "Novel insights into SMYD2 and SMYD3 inhibitors: from potential anti-tumoural therapy to a variety of new applications". Molecular Biology Reports. 48 (11): 7499–7508. doi:10.1007/s11033-021-06701-6. PMID 34510321.
Tang W, Saratzis A, Pattee J, Smith J, Pankratz N, Leavy OC, et al. (January 2020). "Replication of Newly Identified Genetic Associations Between Abdominal Aortic Aneurysm and SMYD2, LINC00540, PCIF1/MMP9/ZNF335, and ERG". European Journal of Vascular and Endovascular Surgery. 59 (1): 92–97. doi:10.1016/j.ejvs.2019.02.017. PMC 6954948. PMID 31680049.
Fabini E, Manoni E, Ferroni C, Rio AD, Bartolini M (April 2019). "Small-molecule inhibitors of lysine methyltransferases SMYD2 and SMYD3: current trends". Future Medicinal Chemistry. 11 (8): 901–921. doi:10.4155/fmc-2018-0380. PMID 30998113.
Padilla A, Manganaro JF, Huesgen L, Roess DA, Brown MA, Crans DC (February 2023). "Targeting Epigenetic Changes Mediated by Members of the SMYD Family of Lysine Methyltransferases". Molecules. 28 (4). Basel, Switzerland: 2000. doi:10.3390/molecules28042000. PMC 9967872. PMID 36838987.
Alshammari E, Zhang YX, Yang Z (August 2022). "Mechanistic and functional extrapolation of SET and MYND domain-containing protein 2 to pancreatic cancer". World Journal of Gastroenterology. 28 (29): 3753–3766. doi:10.3748/wjg.v28.i29.3753. PMC 9367238. PMID 36157542.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000143499 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026603 – 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.

[Zheng_2022-5] 1 2 3 Zheng Q, Zhang W, Rao GW (August 2022). "Protein Lysine Methyltransferase SMYD2: A Promising Small Molecule Target for Cancer Therapy". Journal of Medicinal Chemistry. 65 (15): 10119–10132. doi:10.1021/acs.jmedchem.2c00325. PMID 35914250.

[Yi_2019-6] Yi X, Jiang XJ, Fang ZM (August 2019). "Histone methyltransferase SMYD2: ubiquitous regulator of disease". Clinical Epigenetics. 11 (1) 112. doi:10.1186/s13148-019-0711-4. PMC 6670139. PMID 31370883.

[Spellmon_2015-7] Spellmon N, Holcomb J, Trescott L, Sirinupong N, Yang Z (January 2015). "Structure and function of SET and MYND domain-containing proteins". International Journal of Molecular Sciences. 16 (1): 1406–1428. doi:10.3390/ijms16011406. PMC 4307310. PMID 25580534.

SMYD2

Function

Clinical significance

References

Further reading