Q8R5A0
Gene name |
Smyd2 |
Protein name |
N-lysine methyltransferase SMYD2 |
Names |
Histone methyltransferase SMYD2, SET and MYND domain-containing protein 2 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:226830 |
EC number |
2.1.1.354: Methyltransferases |
Protein Class |
HISTONE-LYSINE N-METHYLTRANSFERASE SMYD (PTHR12197) |
Descriptions
SmyD2 belongs to a new class of chromatin regulators that control gene expression in heart development and tumorigenesis. Besides methylation of histone H3 K4, SmyD2 can methylate non-histone targets including p53. The methyltransferase activity of SmyD proteins has been proposed to be regulated by autoinhibition via the intra- and interdomain bending of the conserved C-terminal domain (CTD). The CTD stabilizes the autoinhibited conformation of SmyD2 and restricts access to the catalytic site.
In addition, the CTD is structurally similar to tetratricopeptide repeats (TPR), a motif through which many cochaperones bind to the heat shock protein Hsp90. The CTD may be important for the activation of SmyD proteins by Hsp90.
Autoinhibitory domains (AIDs)
Target domain |
7-241 (SET domain) |
Relief mechanism |
Partner binding |
Assay |
Structural analysis |
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
3 structures for Q8R5A0
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 3QWV | X-ray | 203 A | A | 1-433 | PDB |
| 3QWW | X-ray | 180 A | A | 1-433 | PDB |
| AF-Q8R5A0-F1 | Predicted | AlphaFoldDB |
12 variants for Q8R5A0
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3388521351 | 99 | N>K | No | EVA | |
| rs3388519439 | 121 | E>G | No | EVA | |
| rs3388526311 | 157 | H>R | No | EVA | |
| rs3388521308 | 280 | R>G | No | EVA | |
| rs3388521121 | 292 | R>L | No | EVA | |
| rs3388525371 | 331 | V>A | No | EVA | |
| rs3388522677 | 339 | M>L | No | EVA | |
| rs13471841 | 362 | Y>* | No | EVA | |
| rs3388521528 | 384 | M>K | No | EVA | |
| rs3388525464 | 410 | A>P | No | EVA | |
| rs3388525766 | 417 | G>D | No | EVA | |
| rs3388525362 | 429 | E>* | No | EVA |
No associated diseases with Q8R5A0
No regional properties for Q8R5A0
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| No domain, repeats, and functional sites for Q8R5A0 | |||
Functions
| Description | ||
|---|---|---|
| EC Number | 2.1.1.354 | Methyltransferases |
| Subcellular Localization |
|
|
| PANTHER Family | PTHR12197 | HISTONE-LYSINE N-METHYLTRANSFERASE SMYD |
| PANTHER Subfamily | PTHR12197:SF193 | N-LYSINE METHYLTRANSFERASE SMYD2 |
| PANTHER Protein Class |
chromatin/chromatin-binding, or -regulatory protein
histone modifying enzyme |
|
| PANTHER Pathway Category | No pathway information available | |
3 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
6 GO annotations of molecular function
| Name | Definition |
|---|---|
| histone H3K36 methyltransferase activity | Catalysis of the reaction |
| histone H3K4 trimethyltransferase activity | Catalysis of the reaction |
| metal ion binding | Binding to a metal ion. |
| p53 binding | Binding to one of the p53 family of proteins. |
| protein-lysine N-methyltransferase activity | Catalysis of the transfer of a methyl group from S-adenosyl-L-methionine to the epsilon-amino group of a lysine residue in a protein substrate. |
| RNA polymerase II complex binding | Binding to an RNA polymerase II core enzyme, a multisubunit eukaryotic nuclear RNA polymerase typically composed of twelve subunits. |
7 GO annotations of biological process
| Name | Definition |
|---|---|
| heart development | The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood. |
| histone lysine methylation | The modification of a histone by addition of one or more methyl groups to a lysine residue. |
| negative regulation of cell population proliferation | Any process that stops, prevents or reduces the rate or extent of cell proliferation. |
| negative regulation of transcription by RNA polymerase II | Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| peptidyl-lysine dimethylation | The methylation of peptidyl-lysine to form peptidyl-N6,N6-dimethyl-L-lysine. |
| peptidyl-lysine monomethylation | The methylation of peptidyl-lysine to form peptidyl-N6-methyl-L-lysine. |
| regulation of DNA damage response, signal transduction by p53 class mediator | Any process that modulates the frequency, rate or extent of the cascade of processes induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, in response to the detection of DNA damage. |
13 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q0P585 | SMYD2 | N-lysine methyltransferase SMYD2 | Bos taurus (Bovine) | SS |
| Q5ZIZ2 | SMYD5 | Histone-lysine N-trimethyltransferase SMYD5 | Gallus gallus (Chicken) | PR |
| E1C5V0 | SMYD2 | N-lysine methyltransferase SMYD2 | Gallus gallus (Chicken) | SS |
| Q6GMV2 | SMYD5 | Histone-lysine N-trimethyltransferase SMYD5 | Homo sapiens (Human) | PR |
| Q9H7B4 | SMYD3 | Histone-lysine N-methyltransferase SMYD3 | Homo sapiens (Human) | EV |
| Q9NRG4 | SMYD2 | N-lysine methyltransferase SMYD2 | Homo sapiens (Human) | SS |
| Q3TYX3 | Smyd5 | Histone-lysine N-trimethyltransferase SMYD5 | Mus musculus (Mouse) | PR |
| Q9CWR2 | Smyd3 | Histone-lysine N-methyltransferase SMYD3 | Mus musculus (Mouse) | SS |
| C3RZA1 | SMYD2 | N-lysine methyltransferase SMYD2 | Sus scrofa (Pig) | SS |
| Q7M6Z3 | Smyd2 | N-lysine methyltransferase SMYD2 | Rattus norvegicus (Rat) | SS |
| P34318 | set-3 | SET domain-containing protein 3 | Caenorhabditis elegans | PR |
| Q5RGL7 | smyd2b | N-lysine methyltransferase SMYD2-B | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q5BJI7 | smyd2a | N-lysine methyltransferase SMYD2-A | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MRAEARGGLE | RFCSAGKGRG | LRALRPFHVG | DLLFSCPAYA | CVLTVGERGH | HCECCFARKE |
| 70 | 80 | 90 | 100 | 110 | 120 |
| GLSKCGRCKQ | AFYCDVECQK | EDWPLHKLEC | SSMVVLGENW | NPSETVRLTA | RILAKQKIHP |
| 130 | 140 | 150 | 160 | 170 | 180 |
| ERTPSEKLLA | VREFESHLDK | LDNEKKDLIQ | SDIAALHQFY | SKYLEFPDHS | SLVVLFAQVN |
| 190 | 200 | 210 | 220 | 230 | 240 |
| CNGFTIEDEE | LSHLGSAIFP | DVALMNHSCC | PNVIVTYKGT | LAEVRAVQEI | HPGDEVFTSY |
| 250 | 260 | 270 | 280 | 290 | 300 |
| IDLLYPTEDR | NDRLRDSYFF | TCECRECTTK | DKDKAKVEVR | KLSSPPQAEA | IRDMVRYARN |
| 310 | 320 | 330 | 340 | 350 | 360 |
| VIEEFRRAKH | YKSPSELLEI | CELSQEKMSS | VFEDSNVYML | HMMYQAMGVC | LYMQDWEGAL |
| 370 | 380 | 390 | 400 | 410 | 420 |
| KYGQKIIKPY | SKHYPVYSLN | VASMWLKLGR | LYMGLENKAA | GEKALKKAIA | IMEVAHGKDH |
| 430 | |||||
| PYISEIKQEI | ESH |