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.
| Symbol | PIN1 |
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| Full Name | Peptidyl-prolyl cis-trans Isomerase NIMA-Interacting 1 |
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| Chromosomal Location | 19p13.13 |
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| NCBI Gene ID | [5300](https://www.ncbi.nlm.nih.gov/gene/5300) |
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| OMIM | [607712](https://www.omim.org/entry/607712) |
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| Ensembl ID | ENSG00000100429 |
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| UniProt ID | [Q13535](https://www.uniprot.org/uniprot/Q13535) |
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| Associated Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Cancer](/diseases/cancer) |
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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.
- 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
- Tau Phosphorylation Regulation: PIN1 binds to phosphorylated tau (p-tau) and promotes proper tau folding, preventing aggregation
- Cell Cycle Regulation: Controls entry and progression through mitosis via regulation of mitotic proteins
- Signal Transduction: Modulates signaling pathways including MAPK, PI3K/AKT, and Wnt/β-catenin
- Transcriptional Regulation: Influences transcription factor activity including p53, c-Jun, and NF-κB
- Protein Quality Control: Aids in proper folding and trafficking of proteins
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)
- Cerebral Cortex: Moderate to high expression, particularly in pyramidal neurons
- Hippocampus: High expression in CA1-CA3 regions and dentate gyrus
- Substantia Nigra: Present in dopaminergic neurons
- Cerebellum: Moderate expression in Purkinje cells
- Nuclear: Predominantly nuclear localization
- Cytoplasmic: Also present in cytoplasm
- Neuronal Processes: Localizes to dendritic spines
| Variant |
Function |
Disease Association |
| S16E |
Polymorphism |
Possible altered activity |
| Q33K |
Polymorphism |
None confirmed |
| H89A |
Loss of function |
Research tool |