PIN1 — Peptidyl-prolyl cis-trans Isomerase NIMA-Interacting 1

PIN1 — Peptidyl-prolyl cis-trans Isomerase NIMA-Interacting 1

Gene Overview

PIN1 (Peptidyl-prolyl cis-trans Isomerase NIMA-Interacting 1) is a peptidyl-prolyl cis-trans isomerase that specifically binds to phosphorylated serine/threonine-proline motifs and catalyzes the isomerization of peptide bonds. PIN1 is a critical regulator of protein function in multiple signaling pathways and has been implicated in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions.

Gene Information

PIN1 — Peptidyl-prolyl cis-trans Isomerase NIMA-Interacting 1

Gene Overview

PIN1 (Peptidyl-prolyl cis-trans Isomerase NIMA-Interacting 1) is a peptidyl-prolyl cis-trans isomerase that specifically binds to phosphorylated serine/threonine-proline motifs and catalyzes the isomerization of peptide bonds. PIN1 is a critical regulator of protein function in multiple signaling pathways and has been implicated in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions.

Gene Information

<div class="infobox infobox-gene">
<table>
<tr><th>Symbol</th><td>PIN1</td></tr>
<tr><th>Full Name</th><td>Peptidyl-prolyl cis-trans Isomerase NIMA-Interacting 1</td></tr>
<tr><th>Chromosomal Location</th><td>19p13.13</td></tr>
<tr><th>NCBI Gene ID</th><td>[5300](https://www.ncbi.nlm.nih.gov/gene/5300)</td></tr>
<tr><th>OMIM</th><td>[607712](https://www.omim.org/entry/607712)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000100429</td></tr>
<tr><th>UniProt ID</th><td>[Q13535](https://www.uniprot.org/uniprot/Q13535)</td></tr>
<tr><th>Associated Diseases</th><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Cancer](/diseases/cancer)</td></tr>
</table>
</div>

Function

PIN1 is a unique peptidyl-prolyl cis-trans isomerase (PPIase) that catalyzes the isomerization of peptide bonds preceding phosphorylated serine or threonine residues. This post-translational modification can dramatically alter protein conformation and function.

Structural Features

• WW Domain: N-terminal domain that recognizes phosphorylated serine/threonine-proline motifs
• PPIase Domain: C-terminal catalytic domain that catalyzes cis-trans isomerization
• Substrate Specificity: Highly specific for pSer/Thr-Pro motifs, unique among PPIases

Biological Functions

Disease Associations

Alzheimer's Disease

PIN1 plays a complex role in AD pathophysiology:

• Beneficial Function: Catalyzes isomerization of phosphorylated tau, promoting proper tau function
• Pathogenic Dysfunction: In AD brain, PIN1 activity is reduced, leading to tau hyperphosphorylation and neurofibrillary tangle formation
• Therapeutic Target: PIN1 activators are being explored as potential AD therapeutics
• Reference: [Lu et al., Science (1999)](https://doi.org/10.1126/science.286.5446.1741)

Parkinson's Disease

• PIN1 levels are altered in PD brains
• May regulate [α-synuclein](/proteins/alpha-synuclein) phosphorylation and aggregation
• Reference: [Sala et al., J. Neurochem. (2009)](https://pubmed.ncbi.nlm.nih.gov/19250338/)

Cancer

• Overexpression in multiple cancers including breast, prostate, and lung
• Promotes cell proliferation and survival
• Reference: [Lu et al., Nat. Rev. Cancer (2009)](https://doi.org/10.1038/nrc2734)

Expression

Brain Expression

• Cerebral [Cortex](/brain-regions/cortex): Moderate to high expression, particularly in pyramidal [neurons](/entities/neurons)
• [Hippocampus](/brain-regions/hippocampus): High expression in CA1-CA3 regions and dentate gyrus
• Substantia Nigra: Present in dopaminergic neurons
• Cerebellum: Moderate expression in Purkinje cells

Cellular Localization

• Nuclear: Predominantly nuclear localization
• Cytoplasmic: Also present in cytoplasm
• Neuronal Processes: Localizes to [dendritic spines](/mechanisms/dendritic-spines)

Common Variants

| Variant | Function | Disease Association |
|---------|----------|---------------------|
| S16E | Polymorphism | Possible altered activity |
| Q33K | Polymorphism | None confirmed |
| H89A | Loss of function | Research tool |

Therapeutic Implications

Drug Development

• PIN1 Activators: Pharmaceutical compounds that enhance PIN1 activity for AD treatment
• PIN1 Inhibitors: Being developed for cancer therapy
• Reference: [Pastorino et al., Nat. Rev. Drug Discov. (2016)](https://doi.org/10.1038/nrd.2016.138)

Biomarker Potential

• PIN1 expression in CSF may serve as a biomarker for neurodegeneration
• Reference: [Matsuda et al., J. Alzheimers Dis. (2015)](https://pubmed.ncbi.nlm.nih.gov/25824923/)

See Also

• [Tau Pathology](/mechanisms/tau-pathology)
• [Protein Phosphorylation](/mechanisms/protein-phosphorylation)
• [Alzheimer's Disease Genes](/diseases/alzheimers#genes)
• [GSK3B](/genes/gsk3b) - Tau kinase
• [CDK5](/genes/cdk5) - Tau kinase
• [PP2A](/genes/pp2a) - Tau phosphatase

References

Pathway Diagram

The following diagram shows the key molecular relationships involving PIN1 — Peptidyl-prolyl cis-trans Isomerase NIMA-Interacting 1 discovered through SciDEX knowledge graph analysis: