SMYD2 (SET and MYND domain containing 2)

2011-05-01   Hitoshi Tsuda , Shuhei Komatsu 

Department 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

Atlas Image

Description

55913 bp, 12 exons.

Transcription

1689 bp mRNA.

Proteins

Atlas Image

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).

Bibliography

Pubmed IDLast YearTitleAuthors
180657562008The tale of two domains: proteomics and genomics analysis of SMYD2, a new histone methyltransferase.Abu-Farha M et al
211037872010Gene trio signatures as molecular markers to predict response to doxorubicin cyclophosphamide neoadjuvant chemotherapy in breast cancer patients.Barros Filho MC et al
168059132006Identification 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
171089712006Repression of p53 activity by Smyd2-mediated methylation.Huang J et al
215095942011Differential expression of a set of genes in follicular and classic variants of papillary thyroid carcinoma.Igci YZ et al
194236492009Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous cell carcinoma.Komatsu S et al
208707192010Methylation 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 IDTranscript IDUniprot
ENSG00000143499ENST00000366957Q9NRG4
ENSG00000143499ENST00000416415B0R0U3

Expression (GTEx)

0
10
20
30
40
50
60
70
80

Pathways

PathwaySourceExternal ID
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
PKMTs methylate histone lysinesREACTOMER-HSA-3214841
Regulation of TP53 ActivityREACTOMER-HSA-5633007
Regulation of TP53 Activity through MethylationREACTOMER-HSA-6804760

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
208707192010Methylation of the retinoblastoma tumor suppressor by SMYD2.93
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
180657562008The tale of two domains: proteomics and genomics analysis of SMYD2, a new histone methyltransferase.72
217824582011Structural basis of substrate methylation and inhibition of SMYD2.72
227874292012RB1 methylation by SMYD2 enhances cell cycle progression through an increase of RB1 phosphorylation.68
194236492009Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous cell carcinoma.65
241015092013Regulation of estrogen receptor α by histone methyltransferase SMYD2-mediated protein methylation.52
220283802011Proteomic analyses of the SMYD family interactomes identify HSP90 as a novel target for SMYD2.50
247261412014The histone methyltransferase SMYD2 methylates PARP1 and promotes poly(ADP-ribosyl)ation activity in cancer cells.36
248800802014SMYD2-dependent HSP90 methylation promotes cancer cell proliferation by regulating the chaperone complex formation.34

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