| PTPRC Protein (CD45) | |
|---|---|
| Protein Name | Protein Tyrosine Phosphatase Receptor Type C |
| Gene | [PTPRC](/genes/ptprc) |
| UniProt ID | [P08575](https://www.uniprot.org/uniprot/P08575) |
| PDB ID | 5ln3, 5cms, 1YJ2 |
| Molecular Weight | 180-220 kDa (various isoforms) |
| Subcellular Localization | Cell membrane (type I transmembrane) |
| Protein Family | Receptor-type PTP family (CD45 family) |
| Expression | All nucleated hematopoietic cells, microglia |
PTPRC (Protein Tyrosine Phosphatase Receptor Type C), more commonly known as CD45, is a receptor-type protein tyrosine phosphatase that plays a central role in regulating immune cell signaling[1]. As the prototypic member of the CD45 family, CD45 is expressed on all nucleated hematopoietic cells and serves as a critical regulator of signal transduction thresholds in immune cells. In the central nervous system, CD45 is expressed primarily on microglia, the resident immune cells of the brain, where it plays essential roles in modulating neuroinflammatory responses and microglial activation states[2].
CD45 is a large transmembrane protein characterized by an heavily glycosylated extracellular domain, a single transmembrane helix, and an intracellular tyrosine phosphatase domain. The protein undergoes extensive alternative splicing, generating multiple isoforms with distinct functions and tissue distributions. This complexity allows CD45 to finetune immune responses in different contexts, including within the brain where microglial CD45 critically influences neurodegenerative disease progression[3].
This comprehensive page covers CD45's molecular structure, its normal functions in the nervous system, its dysregulation in neurodegenerative diseases, and its potential as a therapeutic target.
CD45 possesses a distinctive multi-domain architecture that enables its unique regulatory functions:
Extracellular Domain (aa 1-583):
Transmembrane Region (aa 584-606):
Intracellular Domain (aa 607-1284):
CD45 exists in multiple isoforms generated by alternative splicing:
CD45RO: Short isoform lacking exons 4-6 (extracellular domain)
CD45RA: Long isoform including all exons
CD45RB: Intermediate isoform
CD45RC: Variable isoform
Glycosylation:
Phosphorylation:
CD45 is a master regulator of immune cell signal transduction:
Src Family Kinase Regulation:
Signal Threshold Setting:
Cellular Activation:
In the brain, CD45 performs critical microglial regulatory functions:
Activation State Modulation:
Cytokine Regulation:
Phagocytosis:
CD45 plays a complex role in Alzheimer's disease pathogenesis:
Amyloid Clearance:
Chronic Activation:
Expression Changes:
Neuroinflammation:
Synaptic Dysfunction:
Therapeutic Implications:
CD45 is implicated in Parkinson's disease through microglial pathways:
Dopaminergic Neuron Vulnerability:
Inflammatory Responses:
Mitochondrial Connections:
| Partner Protein | Interaction Type | Functional Consequence |
|---|---|---|
| LCK | Dephosphorylation | T cell activation |
| FYN | Dephosphorylation | Signal initiation |
| SYK | Dephosphorylation | B cell signaling |
| ZAP-70 | Dephosphorylation | TCR signaling |
| Partner | Interaction | Effect |
|---|---|---|
| Tyrosine kinases | Regulation | Activation state |
| Cytokine receptors | Modulation | Inflammatory response |
| Phagocytic receptors | Coordination | Clearance function |
CD45 Knockout Mice:
Conditional Knockouts:
Immunomodulation:
Microglial Targeting:
Specificity:
Complexity:
Thomas ML, et al. The CD45 tyrosine phosphatase: a component of the immunoreceptor signaling complex. Science. 1992. ↩︎
Wyss-Coray T, et al. CD45 in microglia and neurodegeneration: a therapeutic target?. Nature Reviews Neuroscience. 2013. ↩︎
Butters TD, et al. CD45 and immune regulation in the central nervous system. Journal of Neuroimmunology. 2003. ↩︎
Hermiston ML, et al. CD45: a critical regulator of signaling thresholds in immune cells. Immunology Today. 2001. ↩︎
Schwartz M, et al. Microglial activation in neurodegeneration: the role of CD45. Trends in Neurosciences. 2003. ↩︎
Zhu Y, et al. CD45 regulates microglial activation and inflammatory responses. Journal of Neuroinflammation. 2011. ↩︎
Tan J, et al. CD45 deficiency on microglia enhances amyloid clearance in Alzheimer's disease. Journal of Experimental Medicine. 2008. ↩︎
LalANC TA, et al. Microglial CD45 in normal aging and Alzheimer's disease. Glia. 2010. ↩︎
Liu Y, et al. Targeting CD45 for immunotherapy of neurodegenerative diseases. Neuropharmacology. 2014. ↩︎ ↩︎
Zhang W, et al. CD45 and Parkinson's disease: role in microglial activation. Movement Disorders. 2019. ↩︎
Chen L, et al. CD45 polymorphisms and susceptibility to neurodegenerative diseases. Journal of the Neurological Sciences. 2018. ↩︎
Zhou X, et al. CD45 as a biomarker for Alzheimer's disease progression. Alzheimer's and Dementia. 2021. ↩︎