### SMYD2 Gene Summary

**Gene Symbol:** SMYD2  
**Protein Function:** SMYD2 encodes a protein-lysine N-methyltransferase that specifically catalyzes the methylation of both histones and non-histone proteins. It is particularly noted for trimethylating histone H3 at lysine 4 (H3K4me3) and has a stronger methylation activity on the p53 tumor suppressor protein (TP53) and retinoblastoma protein (RB1). SMYD2 monomethylates p53 at lysine 370, decreasing its DNA-binding activity and subsequent transcriptional regulatory functions. Additionally, SMYD2 modifies RB1 by monomethylating it at lysine 860.

### 1. Associated Genes

In addition to p53 (TP53) and RB1, SMYD2 has been associated with:

- **KMT2D**: Histone methyltransferase that could have functional interactions in gene regulation.
- **EZH2**: Another histone methyltransferase that may play a role in related pathways.
  
It’s important to note that while these genes may not be directly methylated by SMYD2, they are often involved in similar pathways related to cancer and cellular signaling.

### 2. Aging and Age-related Diseases

SMYD2 has been implicated in the regulation of cellular processes that may impact aging and age-related diseases, including:

- **Cancer**: As a regulator of p53 and RB1, SMYD2's activity can influence tumorigenesis. Dysregulation of SMYD2 has been associated with various cancers, indicating its potential role in tumor progression in aging tissues.
- **Cardiovascular Diseases**: Research suggests that alterations in methylation patterns, including those mediated by SMYD2, may affect cardiac function and diseases associated with aging.
  
The role of SMYD2 in epigenetic modifications ties it to processes of cellular senescence and could affect age-related decline in tissue regeneration.

### 3. Drug Interactions

While specific drugs targeting SMYD2 directly are not extensively characterized, there are potential interactions with drugs affecting histone methylation or cellular pathways involving SMYD2:

- **Inhibitors of Histone Methyltransferases**: Such as those in clinical trials targeting EZH2 or other similar enzymes.
- **Anticancer agents**: Since SMYD2 influences p53, agents that restore p53 function, such as MDM2 inhibitors, could play a role alongside SMYD2 modifications.

### 4. Pathways and Biological Processes

SMYD2 is involved in several crucial biological processes and pathways, including:

- **Histone Methylation**: Regulates chromatin structure and gene expression through the modification of histones.
- **Cell Cycle Regulation**: By altering RB1 and p53, it plays a role in the control of the cell cycle and apoptosis.
- **Tumorigenesis**: Through modifications of tumor suppressor proteins, contributions to cancer development and progression.
- **Cellular Response to Stress**: By modifying proteins involved in cell survival and apoptosis, SMYD2 could play a role in responses to various stressors, including oxidative stress.

### Conclusion

The SMYD2 gene plays a significant role in epigenetic regulation through its ability to methylate histones and non-histone proteins, with important implications for cancer progression and cellular aging. Further studies are necessary to clarify its role in age-related diseases and potential therapeutic avenues.