ADAM9 Protein — Disintegrin and Metalloproteinase Domain 9

ADAM9 Protein — Disintegrin and Metalloproteinase Domain 9

Introduction

Adam9 Protein — Disintegrin And Metalloproteinase Domain 9 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

<div class="infobox infobox-protein">
<h3>ADAM9 Protein</h3>
<table>
<tr><th>Protein Name</th><td>Disintegrin and Metalloproteinase Domain 9</td></tr>
<tr><th>Gene</th><td>[ADAM9](/genes/adam9)</td></tr>
<tr><th>UniProt ID</th><td>[Q13443](https://www.uniprot.org/uniprot/Q13443)</td></tr>
<tr><th>Protein Size</th><td>819 amino acids (~90 kDa)</td></tr>
<tr><th>Subcellular Localization</th><td>Cell surface; membrane-anchored; shed to soluble form</td></tr>
<tr><th>Protein Family</th><td>ADAM family (A Disintegrin And Metalloproteinase)</td></tr>
<tr><th>PDB Structures</th><td>[1JXK](https://www.ebi.ac.uk/pdbe/search/pdb/1JXK), [2EAO](https://www.ebi.ac.uk/pdbe/search/pdb/2EAO)</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

ADAM9 (A Disintegrin and Metalloproteinase 9) is a member of the ADAM family of transmembrane metalloproteinases that plays important roles in cell adhesion, migration, and proteolytic processing of various substrates, including the [amyloid precursor protein](/entities/app-protein) (APP).

Structure

ADAM9 has the characteristic multi-domain structure of ADAM proteins:

ADAM9 Protein — Disintegrin and Metalloproteinase Domain 9

Introduction

Adam9 Protein — Disintegrin And Metalloproteinase Domain 9 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

<div class="infobox infobox-protein">
<h3>ADAM9 Protein</h3>
<table>
<tr><th>Protein Name</th><td>Disintegrin and Metalloproteinase Domain 9</td></tr>
<tr><th>Gene</th><td>[ADAM9](/genes/adam9)</td></tr>
<tr><th>UniProt ID</th><td>[Q13443](https://www.uniprot.org/uniprot/Q13443)</td></tr>
<tr><th>Protein Size</th><td>819 amino acids (~90 kDa)</td></tr>
<tr><th>Subcellular Localization</th><td>Cell surface; membrane-anchored; shed to soluble form</td></tr>
<tr><th>Protein Family</th><td>ADAM family (A Disintegrin And Metalloproteinase)</td></tr>
<tr><th>PDB Structures</th><td>[1JXK](https://www.ebi.ac.uk/pdbe/search/pdb/1JXK), [2EAO](https://www.ebi.ac.uk/pdbe/search/pdb/2EAO)</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

ADAM9 (A Disintegrin and Metalloproteinase 9) is a member of the ADAM family of transmembrane metalloproteinases that plays important roles in cell adhesion, migration, and proteolytic processing of various substrates, including the [amyloid precursor protein](/entities/app-protein) (APP).

Structure

ADAM9 has the characteristic multi-domain structure of ADAM proteins:

• N-terminal Signal Sequence: Targets protein to secretory pathway
• Prodomain: Keeps the enzyme inactive until processed
• Metalloproteinase Domain: Contains the catalytic zinc (HExGHNLG) motif; responsible for proteolytic activity
• Disintegrin Domain: Mediates cell-cell adhesion through interactions with integrin receptors
• Cysteine-rich Region: Contains additional adhesion sites
• Epidermal Growth Factor (EGF)-like Domain: Present in some ADAMs
• Transmembrane Domain: Anchors protein to plasma membrane
• Cytoplasmic Tail: Contains signaling motifs and sorting information

Normal Function

In normal cells, ADAM9 participates in:

Role in Disease

Alzheimer's Disease

ADAM9 is one of the alpha-secretase candidates that can cleave APP within the [amyloid-beta](/proteins/amyloid-beta) sequence, potentially preventing amyloid plaque formation^[1]. However, ADAM9 also:

• Can generate amyloidogenic fragments under certain conditions
• Is upregulated in AD brains, possibly as a compensatory response
• Contributes to altered synaptic function in AD

Cancer

ADAM9 is overexpressed in various cancers and promotes:

• Tumor invasion and metastasis
• Angiogenesis
• Resistance to chemotherapy

Cardiovascular Disease

ADAM9 plays roles in atherosclerosis, restenosis, and heart failure.

Therapeutic Targeting

ADAM9 is a potential therapeutic target:

• Selective Inhibitors: Metalloproteinase inhibitors that specifically target ADAM9
• Monoclonal Antibodies: Blocking antibodies that prevent substrate cleavage
• Small Molecule Inhibitors: Broad-spectrum MMP/ADAM inhibitors with ADAM9 selectivity

Interactions

ADAM9 interacts with:

• APP: Cleaves APP at alpha-secretase site
• Integrins: α6β1, αvβ3 - for cell adhesion
• TGF-α: Growth factor substrate
• Notch: Proteolytic processing
• Fibronectin: Extracellular matrix protein

See Also

• [ADAM9 Gene](/genes/adam9)
• [APP Processing Pathways](/mechanisms/app-processing)
• [Alpha-Secretase](/proteins/adam10-protein)
• [ADAM Family](/proteins/adam17-protein)
• [ADAM9 in Alzheimer's Disease](/diseases/alzheimers-disease)

Background

The study of Adam9 Protein — Disintegrin And Metalloproteinase Domain 9 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

PMID: 14600253(https://pubmed.ncbi.nlm.nih.gov/14600253/)