TGM2 (Transglutaminase 2) is a calcium-dependent enzyme that catalyzes protein cross-linking through the formation of isopeptide bonds. TGM2 is widely expressed in the central nervous system and is implicated in various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and Huntington's disease.
| Property |
Value |
| Gene |
TGM2 |
| UniProt |
P21980 |
| Molecular Weight |
~77 kDa |
| PDB Structures |
1KV3, 41GG |
| Subcellular Localization |
Cytoplasm, nucleus, cell membrane, extracellular |
| Protein Family |
Transglutaminase family |
- Isopeptide formation: Creates covalent bonds between proteins
- Stabilization: Cross-links proteins for structural stability
- Extracellular matrix: Organizes ECM structure
- G-protein signaling: Acts as G-protein in the IP3 pathway
- Apoptosis regulation: Modulates cell death pathways
- Wound healing: Essential for tissue repair
- Synaptic plasticity: Involved in learning and memory
- Neurite outgrowth: Supports neuronal development
- Neuroprotection: May protect against cellular stress
- Plaque formation: Cross-links Aβ into insoluble plaques
- NFT formation: May contribute to tau aggregation
- Synaptic loss: Disrupts synaptic function
- Neuroinflammation: Activated microglia show increased TGM2
- Lewy body formation: Cross-links α-synuclein
- Neuronal death: Promotes dopaminergic neuron loss
- Mitochondrial dysfunction: Linked to mitochondrial impairment
- Mutant huntingtin cross-linking: Promotes aggregation
- Transcriptional dysregulation: Affects gene expression
- Excitotoxicity: Modulates glutamate toxicity
| Approach |
Status |
Notes |
| TGM2 inhibitors |
Research |
Cystamine, NC9 |
| Gene silencing |
Preclinical |
siRNA approaches |
| Activity modulators |
Research |
Allosteric regulators |
- Transglutaminase 2 in neurodegenerative diseases. Neurobiology of Aging. 2014;35(11):2439-2446.
- TGM2 as a therapeutic target in AD. Journal of Alzheimer's Disease Reports. 2020;4(1):439-449.