PECAM1 Protein
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">PECAM1 Protein</th>
</tr>
<tr>
<td class="label">
Protein Name</td>
<td>Platelet Endothelial Cell Adhesion Molecule 1</td>
</tr>
<tr>
<td class="label">
Gene Symbol</td>
<td>PECAM1</td>
</tr>
<tr>
<td class="label">
Protein Length</td>
<td>738 amino acids</td>
</tr>
<tr>
<td class="label">
Molecular Weight</td>
<td>~72 kDa (unglycosylated); 80-90 kDa (glycosylated)</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>P16284</td>
</tr>
<tr>
<td class="label">
PDB Structures</td>
<td>1FNS, 1HTH, 2KBC, 4CYT</td>
</tr>
<tr>
<td class="label">
Cellular Location</td>
<td>Plasma membrane (type I transmembrane); cell junctions</td>
</tr>
<tr>
<td class="label">
Protein Family</td>
<td>Immunoglobulin superfamily (IgSF)</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">
Integrin αvβ3</td>
<td>Heterophilic</td>
</tr>
<tr>
<td class="label">
Integrin α6β1</td>
<td>Heterophilic</td>
</tr>
<tr>
<td class="label">
CD38</td>
<td>Heterophilic</td>
</tr>
<tr>
<td class="label">
Glycosaminoglycans</td>
<td>Heterophilic</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">
Blocking Antibodies</td>
<td>Anti-PECAM1 antibodies</td>
</tr>
<tr>
<td class="label">**Peptide Inhib
...PECAM1 Protein
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">PECAM1 Protein</th>
</tr>
<tr>
<td class="label">
Protein Name</td>
<td>Platelet Endothelial Cell Adhesion Molecule 1</td>
</tr>
<tr>
<td class="label">
Gene Symbol</td>
<td>PECAM1</td>
</tr>
<tr>
<td class="label">
Protein Length</td>
<td>738 amino acids</td>
</tr>
<tr>
<td class="label">
Molecular Weight</td>
<td>~72 kDa (unglycosylated); 80-90 kDa (glycosylated)</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>P16284</td>
</tr>
<tr>
<td class="label">
PDB Structures</td>
<td>1FNS, 1HTH, 2KBC, 4CYT</td>
</tr>
<tr>
<td class="label">
Cellular Location</td>
<td>Plasma membrane (type I transmembrane); cell junctions</td>
</tr>
<tr>
<td class="label">
Protein Family</td>
<td>Immunoglobulin superfamily (IgSF)</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">
Integrin αvβ3</td>
<td>Heterophilic</td>
</tr>
<tr>
<td class="label">
Integrin α6β1</td>
<td>Heterophilic</td>
</tr>
<tr>
<td class="label">
CD38</td>
<td>Heterophilic</td>
</tr>
<tr>
<td class="label">
Glycosaminoglycans</td>
<td>Heterophilic</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">
Blocking Antibodies</td>
<td>Anti-PECAM1 antibodies</td>
</tr>
<tr>
<td class="label">
Peptide Inhibitors</td>
<td>ITIM mimetics</td>
</tr>
<tr>
<td class="label">
Soluble PECAM1</td>
<td>Recombinant sPECAM1</td>
</tr>
<tr>
<td class="label">
Gene Therapy</td>
<td>siRNA/shRNA</td>
</tr>
<tr>
<td class="label">
Kinase Inhibitors</td>
<td>Src family inhibitors</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/coronary-artery-disease" style="color:#ef9a9a">Coronary Artery Disease</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">38 edges</a></td>
</tr>
</table>
Introduction
Pecam1 Protein 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
Platelet Endothelial Cell Adhesion Molecule 1 (PECAM1) is a 738-amino acid type I transmembrane glycoprotein expressed predominantly on endothelial cells, platelets, and leukocytes[@newman1990]. It plays essential roles in vascular inflammation, leukocyte transmigration, and maintaining endothelial barrier function. PECAM1 is particularly concentrated at endothelial cell junctions where it contributes to the formation and maintenance of the endothelial barrier[@muller1989].
Domain Structure
PECAM1 contains distinct structural domains[@stockinger1990]:
Extracellular Domain (19-574 aa)
- Ig-like domain D1 (19-99 aa): N-terminal domain mediating homophilic binding[@wang2005]
- Ig-like domain D2 (100-186 aa): Contributes to adhesion
- Ig-like domain D3 (187-273 aa): Stabilizes D1-D2 interaction
- Ig-like domain D4 (274-363 aa): Provides structural flexibility
- Ig-like domain D5 (364-455 aa): Contains carbohydrate recognition sites
- Ig-like domain D6 (456-574 aa): C-terminal extracellular domain
Transmembrane Domain (575-599 aa)
- Single α-helical membrane-spanning segment
- Contains a cysteine residue for potential palmitoylation
Cytoplasmic Tail (600-738 aa)
- Contains two ITIM (Immunoreceptor Tyrosine-based Inhibitory Motif) sequences[@jackson1997]
- Serine/threonine-rich regions for phosphorylation
- Critical for intracellular signaling
Molecular Function
Homophilic Interactions
PECAM1 mediates homophilic (PECAM1-PECAM1) adhesion[@muller1989][@delisser1997]:
- Endothelial junctions: Concentrated at cell-cell contacts
- Transendothelial migration: Mediates leukocyte passage through endothelium[@muller2011]
- Barrier maintenance: Strengthens endothelial cell junctions[@privratsky2010]
Heterophilic Interactions
PECAM1 also binds to other molecules[@buckley1996]:
Signaling Functions
The cytoplasmic ITIM motifs recruit phosphatases[@jackson1997]:
- SHP-1: Negative regulator of signaling
- SHP-2: Modulates cell activation
- Negative regulation: Maintains immune cell homeostasis
Post-Translational Modifications
Phosphorylation
The cytoplasmic tail contains tyrosine and serine/threonine residues[@zhou2007]:
- Tyrosine phosphorylation: Activates ITIM signaling
- Serine/threonine phosphorylation: Modulates protein function
Glycosylation
PECAM1 is N-glycosylated[@zhang2002]:
- Affects protein folding and stability
- Influences homophilic binding
- Modulates immune recognition
Proteolytic Processing
- Shedding: Metalloproteinase-mediated release of soluble PECAM1 (sPECAM1)[@goldberger1994]
- Soluble form: Elevated in inflammatory conditions
Structural Insights
Crystal Structures
Key structural studies reveal[@wang2005][@caligiuri2003]:
- 1FNS: PECAM1 D1 domain structure
- 1HTH: PECAM1 D1-D2 complex
- 2KBC: Full extracellular domain NMR structure
- Ig-like domains: Arrangement allows flexibility at junctions
- ITIM motifs: Conserved sequences for phosphatase recruitment
- Dimerization: May form trans-homophilic dimers at cell contacts[@paddenberg2003]
Role in Neurodegenerative Diseases
Alzheimer's Disease (AD)
PECAM1 plays complex roles in AD pathophysiology[@kalinowska2008][@grammas2011]:
- BBB dysfunction: Elevated in AD brain microvasculature; contributes to blood-brain barrier breakdown[@zlokovic2008]
- Cerebral amyloid angiopathy (CAA): Associated with vascular amyloid deposits[@weller2009]
- Endothelial activation: Markers correlate with disease severity[@blasko2000]
- Perivascular inflammation: Facilitates perivascular immune cell infiltration[@michaud2013]
- Neurovascular coupling: Dysregulation affects blood flow regulation[@iadecola2017]
Parkinson's Disease (PD)
In PD, PECAM1 contributes to neuroinflammation[@chen2019][@zhang2019]:
- Substantia nigra: Increased expression in dopaminergic regions[@mcgeer1988]
- Microglial activation: Mediates communication between endothelial cells and [microglia](/entities/microglia)[@nottet1996]
- [Blood-brain barrier](/entities/blood-brain-barrier): Contributes to BBB permeability in PD[@kortekaas2005]
- Disease severity: Soluble PECAM1 levels correlate with motor symptoms[@hall2012]
Stroke and Ischemic Injury
PECAM1 is critically involved in stroke pathophysiology[@zhang1998][@wang2004]:
- Ischemic injury: Rapidly upregulated after cerebral ischemia[@zhang1997]
- Reperfusion injury: Mediates post-ischemic inflammation[@petty2009]
- Angiogenesis: Involved in post-stroke blood vessel formation[@hayashi2004]
- Therapeutic target: Blocking PECAM1 reduces infarct size[@ma1999]
Multiple Sclerosis (MS)
PECAM1 participates in MS pathogenesis[@lee1999][@engelhardt2010]:
- Immune cell trafficking: Mediates leukocyte entry into CNS[@raine1995]
- Lesion formation: Elevated in active demyelinating lesions[@cannella1998]
- BBB integrity: Maintains blood-brain barrier function[@lyck2008]
- Endothelial repair: Involved in lesion recovery[@zgraggen2000]
Vascular Dementia
PECAM1 contributes to vascular cognitive impairment[@toledo2013][@iadecola2013]:
- Endothelial dysfunction: Marker of cerebrovascular pathology
- Cerebral hypoperfusion: Contributes to reduced cerebral blood flow
- White matter lesions: Associated with small vessel disease
- Mixed pathology: Common comorbidity with AD
Expression and Regulation
Cellular Expression
- Endothelial cells: High expression, especially at intercellular junctions[@muller1989]
- Platelets: Abundant on platelet surface[@newman1989]
- Leukocytes: Variable; highest on monocytes, neutrophils[@demeure2000]
- Stem cells: Expressed on hematopoietic stem cells
Regulatory Mechanisms
- [NF-κB](/entities/nf-kb): Primary transcriptional regulator[@mahmood1999]
- Cytokines: TNF-α, IL-1β upregulate expression
- Shear stress: Laminar flow maintains; disturbed flow reduces[@chiu2004]
- Hypoxia: Induces PECAM1 expression[@chiu2005]
Therapeutic Targeting
Diagnostic and Prognostic Value
Biomarker Applications
- Soluble PECAM1: Elevated in various neurological conditions[@ridker1998]
- Platelet activation: PECAM1 shedding indicates platelet activation[@michelson1996]
- Endothelial injury: Marker of vascular damage
- Disease monitoring: Levels track with disease progression[@hall2012]
Research Applications
- Endothelial signaling: Model system for ITIM signaling
- Leukocyte trafficking: Key molecule for diapedesis studies
- Mechanotransduction: Model for shear stress sensing
See Also
- [ICAM1 Protein](/proteins/icam1-protein) - Intercellular Adhesion Molecule 1
- [VCAM1 Protein](/proteins/vcam1-protein) - Vascular Cell Adhesion Molecule 1
- [CD38 Protein](/proteins/cd38-protein) - CD38 Molecule
- [Integrin αvβ3 Protein](/proteins/itgav-protein) - Integrin Alpha V
- [Neuroinflammation Pathway](/mechanisms/neuroinflammation-pathway)
- [Blood-Brain Barrier Dysfunction](/mechanisms/blood-brain-barrier-dysfunction)
- [Leukocyte Extravasation Signaling](/mechanisms/leukocyte-extravasation)
- [Coagulation Cascade](/mechanisms/coagulation-cascade)
Background
The study of Pecam1 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
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[Muller WA, et al, (1989) (1989)](https://pubmed.ncbi.nlm.nih.gov/2687648/)
[Stockinger H, et al, (1990) (1990)](https://pubmed.ncbi.nlm.nih.gov/2157696/)
[Wang J, et al, (2005) (2005)](https://pubmed.ncbi.nlm.nih.gov/15893701/)
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