TGF-β Receptor 2 (TGFBR2) Protein

TGF-β Receptor 2 (TGFBR2) Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">TGF-β Receptor 2 (TGFBR2) Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>TGF-β Receptor 2</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>TGFBR2</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P37173</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>70 kDa</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>565 amino acids</td>
</tr>
<tr>
<td class="label">PDB Structures</td>
<td>1M9X, 2B3H, 2PJY, 3K70</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane, endosomes</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

TGF-β Receptor 2 (TGFBR2) is a transmembrane serine/threonine kinase that serves as the primary type II receptor for transforming growth factor-beta ligands in the nervous system. This protein plays critical roles in initiating TGF-β signaling that regulates neuroinflammation, neuronal survival, synaptic plasticity, and glial function.

Overview

TGF-β Receptor 2 (TGFBR2) Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">TGF-β Receptor 2 (TGFBR2) Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>TGF-β Receptor 2</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>TGFBR2</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P37173</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>70 kDa</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>565 amino acids</td>
</tr>
<tr>
<td class="label">PDB Structures</td>
<td>1M9X, 2B3H, 2PJY, 3K70</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane, endosomes</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

TGF-β Receptor 2 (TGFBR2) is a transmembrane serine/threonine kinase that serves as the primary type II receptor for transforming growth factor-beta ligands in the nervous system. This protein plays critical roles in initiating TGF-β signaling that regulates neuroinflammation, neuronal survival, synaptic plasticity, and glial function.

Overview

TGFBR2 (Transforming Growth Factor Beta Receptor 2) is a 70 kDa transmembrane receptor kinase that initiates TGF-β signaling by binding TGF-β ligands and phosphorylating type I receptors (TGFBR1)[@massague2000]. As the primary type II receptor, TGFBR2 is constitutively active and essential for all downstream TGF-β signaling in the nervous system[@heldin2021].

Protein Information

Protein Structure

Extracellular Domain (1-184 aa)

The extracellular domain contains:

• N-terminal domain: Ligand recognition and binding
• cysteine-rich (CR) region: Mediates receptor oligomerization
• cysteine tandem repeat: Characteristic of TGF-β receptor family

Transmembrane Domain (185-207 aa)

Single-pass alpha-helical transmembrane domain anchors the receptor in the plasma membrane.

Kinase Domain (208-565 aa)

The cytoplasmic serine/threonine kinase domain contains:

• Kinase subdomain: Conserved serine/threonine kinase catalytic domain
• C-terminal tail: Regulatory sequences

Normal Function in the Nervous System

TGF-β Signal Initiation

Functions in CNS

• Neuroinflammation regulation: Controls microglial activation and cytokine production[@brionne2021]
• Neuronal survival: Mediates TGF-β-induced neuroprotective effects[@kane2018]
• Synaptic plasticity: Modulates excitatory synaptic transmission[@ferguson2019]
• [Blood-brain barrier](/entities/blood-brain-barrier): Regulates endothelial cell junction integrity[@tichauer2020]
• Oligodendrocyte function: Important for myelination andOPC differentiation[@palazuelos2021]

Role in Disease

Alzheimer's Disease

• TGFBR2 signaling is altered in AD brain, particularly near amyloid plaques[@caraci2021]
• TGF-β/TGFBR2 signaling important for microglial phagocytosis of [Aβ](/proteins/amyloid-beta)[@wysscoray2020]
• Genetic variants in TGFBR2 associated with AD risk[@mousseau2021]

Parkinson's Disease

• TGFBR2 protects dopaminergic [neurons](/entities/neurons) from oxidative stress[@rai2022]
• TGF-β signaling modulates [alpha-synuclein](/proteins/alpha-synuclein) toxicity through TGFBR2[@reynolds2021]
• Reduced TGFBR2 expression in PD substantia nigra[@tong2019]

Amyotrophic Lateral Sclerosis

• TGFBR2 signaling influences motor neuron survival[@dormann2020]
• Altered TGF-β pathway in ALS motor [cortex](/brain-regions/cortex) and spinal cord[@ilieva2019]

Multiple Sclerosis

• TGFBR2 critical for oligodendrocyte progenitor cell (OPC) proliferation and differentiation[@palazuelos2021a]
• Implicated in demyelination and remyelination processes[@mcqueen2020]

Therapeutic Targeting

Kinase Inhibitors

• LY2109761: Dual TGFBR1/2 inhibitor in clinical trials[@zhang2019]
• SB-431542: Potent TGFBR2 inhibitor[@inman2002]

Receptor Agonists

• TGF-β1: Endogenous ligand activating TGFBR2 signaling[@sakauchi2021]
• Recombinant TGF-β: Being explored for neuroprotective applications[@akhurst2021]

Key Publications

See Also

• [TGFBR2 Gene](/genes/tgfrb2)
• [TGFBR1 Gene](/genes/tgfrb1)
• [TGFBR1 Protein](/proteins/tgfrb1-protein)
• [SMAD2 Protein](/proteins/smad2-protein)
• [SMAD3 Protein](/proteins/smad3-protein)
• [TGF-β Signaling Pathway](/mechanisms/tgf-beta-signaling-pathway)

Background

The study of Tgf Β Receptor 2 (Tgfbr2) Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
• [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
• [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

References