SMYD2 (SET and MYND domain containing 2)
2011-05-01 Hitoshi Tsuda , Shuhei Komatsu AffiliationDepartment of Pathology, Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan (HT); Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan (SK)
Identity
HGNC
LOCATION
1q32.3
LOCUSID
ALIAS
HSKM-B,KMT3C,ZMYND14
FUSION GENES
DNA/RNA
Description
55913 bp, 12 exons.
Transcription
1689 bp mRNA.
Proteins
Description
433 amino acids. The protein contains SET domain, MYND domain/zinc-finger motif, and cysteine-rich post-SET domain. The SET domain is split into two segments by a MYND domain.
Expression
Wide, highly expressed in heart, brain, liver, kidney, thymus, ovary, embryonic tissues (heart, hypothalamus) (Brown et al., 2006).
Localisation
Cytoplasmic and nucleus (Brown et al., 2006).
Function
Regulation of transcription as a lysine methyltransferase for histone 3, lysine 36 (H3K36) and inhibition of p53s transactivation activity as a lysine methyltransferase for lysine 370 (K370) of p53 through the SET domain (Brown et al., 2006; Huang et al., 2006). Possibly promotion of cell proliferation and/or differentiation through its overexpression/activation-induced inhibition of p53s transactivation activity. Methylation of retinoblastoma (RB) tumor suppressor at lysine 860, that is regulated during cell cycle progression, cellular differentiation ,and in response to DNA damage (Saddic et al., 2010). RB monomethylation at lysine 860 provides a direct binding site for the transcription repressor L3MBTL1. Through interaction with HSP90alpha, SMYD2 histone methyltransferase activity and specificity for histone H3 at lysine 4 (H3K4) are enhanced in vitro (Abu-Farha et al., 2008). SMYD2 gain of function is correlated with the upregulation of 37 and down regulation of 4 genes, the majority of which are involved in the cell cycle, chromatin remodelling, and transcriptional regulation (Abu-Farha et al., 2008).
Homology
Xenopus laevis, Zebrafish, Chicken, Gray short-tailed opossum, Mouse, Rat, Rabbit, Pig, Horse, Cattle, Dog, White-tufted-ear marmoset, Rhesus monkey, Sumatran orangutan, Chimpanzee.
Mutations
Note
Not found.
Implicated in
Entity name
Esophageal squamous cell carcinoma (ESCC)
Note
Frequent overexpression of SMYD2 mRNA and protein was observed in KYSE150 cells with remarkable amplification at 1q32-q41.1 and other ESCC cell lines (11/43 lines, 25.6%). Overexpression of SMYD2 protein was frequently detected in primary tumor samples of ESCC (117/153 cases, 76.5%) as well and significantly correlated with gender, venous invasion, the pT category in the tumor-lymph node-metastasis classification and status of recurrence. Patients with SMYD2-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors. Knockdown of SMYD2 expression inhibited and ectopic overexpression of SMYD2 promoted the proliferation of ESCC cells in a TP53 mutation-independent but SMYD2 expression dependent manner (Komatsu et al., 2009).
Entity name
Thyroid carcinoma and benign thyroid nodule
Note
Using differential display-polymerase chain reaction method, the gene expression differences between benign thyroid nodules (BTNs) and follicular and classic variants of papillary thyroid carcinoma (PTC) were evaluated in a group of 42 patients (15 BTNs, 14 follicular variant of PTC and 13 classic variant of PTC). SMYD2 had lower expression in both carcinoma groups than in BTNs (Igci et al., 2011).
Entity name
Breast cancer
Note
Expression of a group of three genes (MTSS1, RPL37, and SMYD2) evaluated by real-time PCR was shown to be a potential candidate to predict response to neoadjuvant chemotherapy (4 cycles of doxorubicin and cyclophosphamide) in breast cancer patients (Barros Filho et al., 2010).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 18065756 | 2008 | The tale of two domains: proteomics and genomics analysis of SMYD2, a new histone methyltransferase. | Abu-Farha M et al |
| 21103787 | 2010 | Gene trio signatures as molecular markers to predict response to doxorubicin cyclophosphamide neoadjuvant chemotherapy in breast cancer patients. | Barros Filho MC et al |
| 16805913 | 2006 | Identification and characterization of Smyd2: a split SET/MYND domain-containing histone H3 lysine 36-specific methyltransferase that interacts with the Sin3 histone deacetylase complex. | Brown MA et al |
| 17108971 | 2006 | Repression of p53 activity by Smyd2-mediated methylation. | Huang J et al |
| 21509594 | 2011 | Differential expression of a set of genes in follicular and classic variants of papillary thyroid carcinoma. | Igci YZ et al |
| 19423649 | 2009 | Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous cell carcinoma. | Komatsu S et al |
| 20870719 | 2010 | Methylation of the retinoblastoma tumor suppressor by SMYD2. | Saddic LA et al |
Other Information
Locus ID:
NCBI: 56950
MIM: 610663
HGNC: 20982
Ensembl: ENSG00000143499
Variants:
dbSNP: 56950
ClinVar: 56950
TCGA: ENSG00000143499
COSMIC: SMYD2
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000143499 | ENST00000366957 | Q9NRG4 |
| ENSG00000143499 | ENST00000416415 | B0R0U3 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38243079 | 2024 | Lysine methyltransferase SMYD2 enhances androgen receptor signaling to modulate CRPC cell resistance to enzalutamide. | 0 |
| 38740816 | 2024 | Methylation of ESCRT-III components regulates the timing of cytokinetic abscission. | 0 |
| 38243079 | 2024 | Lysine methyltransferase SMYD2 enhances androgen receptor signaling to modulate CRPC cell resistance to enzalutamide. | 0 |
| 38740816 | 2024 | Methylation of ESCRT-III components regulates the timing of cytokinetic abscission. | 0 |
| 36191822 | 2023 | The lysine methyltransferases SET and MYND domain containing 2 (Smyd2) and Enhancer of Zeste 2 (Ezh2) co-regulate osteoblast proliferation and mineralization. | 3 |
| 36912291 | 2023 | SMYD2 Expression: Its Relationship to Cytogenetic and Prognosis in a Newly Diagnosed Childhood B-Acute Lymphoblastic Leukemia. | 0 |
| 37036190 | 2023 | Targeting SMYD2 inhibits prostate cancer cell growth by regulating c-Myc signaling. | 0 |
| 36191822 | 2023 | The lysine methyltransferases SET and MYND domain containing 2 (Smyd2) and Enhancer of Zeste 2 (Ezh2) co-regulate osteoblast proliferation and mineralization. | 3 |
| 36912291 | 2023 | SMYD2 Expression: Its Relationship to Cytogenetic and Prognosis in a Newly Diagnosed Childhood B-Acute Lymphoblastic Leukemia. | 0 |
| 37036190 | 2023 | Targeting SMYD2 inhibits prostate cancer cell growth by regulating c-Myc signaling. | 0 |
| 32342276 | 2022 | SMYD2 facilitates cancer cell malignancy and xenograft tumor development through ERBB2-mediated FUT4 expression in colon cancer. | 7 |
| 35455942 | 2022 | SMYD2 Inhibition Downregulates TMPRSS2 and Decreases SARS-CoV-2 Infection in Human Intestinal and Airway Epithelial Cells. | 6 |
| 35553018 | 2022 | Overexpression of MCAM induced by SMYD2-H3K36me2 in breast cancer stem cell properties. | 0 |
| 35637161 | 2022 | SMYD2 epigenetically activates MEX3A and suppresses CDX2 in colorectal cancer cells to augment cancer growth. | 0 |
| 35939202 | 2022 | STUB1-SMYD2 Axis Regulates Drug Resistance in Glioma cells. | 2 |
Citation
Hitoshi Tsuda ; Shuhei Komatsu
SMYD2 (SET and MYND domain containing 2)
Atlas Genet Cytogenet Oncol Haematol. 2011-05-01
Online version: http://atlasgeneticsoncology.org/gene/47098/smyd2-(set-and-mynd-domain-containing-2)
