PPP1R1A
Protein Phosphatase 1 Regulatory Inhibitor Subunit 1A
Gene Information Card
| Symbol | PPP1R1A |
|---|---|
| Full Name | Protein Phosphatase 1 Regulatory Inhibitor Subunit 1A |
| Gene Type | protein-coding |
| Chromosomal Location | 12q13.2 |
| NCBI Gene ID | 5502 ncbi.nlm.nih.gov/gene/5502 |
| Ensembl ID | ENSG00000135446 |
| UniProt ID | Q13526 |
| OMIM ID | 604999 |
| HGNC ID | 9281 |
| Aliases | DARPP-32, DARPP32 |
Description
PPP1R1A encodes the protein DARPP-32 (dopamine- and cAMP-regulated neuronal phosphoprotein), a key inhibitor of protein phosphatase 1 (PP1). It is highly expressed in the brain, particularly in striatal neurons, and integrates dopaminergic and glutamatergic signaling. Phosphorylation at Thr34 by PKA converts DARPP-32 into a potent PP1 inhibitor, modulating synaptic plasticity and neurotransmission.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Altered DARPP-32 phosphorylation affects dopamine signaling and synaptic plasticity | PMID: 16936726 |
| Parkinson's disease | Dysregulation of DARPP-32 in striatal neurons contributes to motor deficits | PMID: 12626639 |
| Addiction | DARPP-32 mediates responses to drugs of abuse (e.g., cocaine, amphetamine) | PMID: 11729101 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Brain (caudate nucleus) | 18.2 | High |
| Testis | 1.2 | Low |
| Heart | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 3.4 | Neuronal model |
| HEK293 | 0.8 | Low expression |
| U-87 MG | 1.1 | Glioblastoma line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.01% | Alters phosphorylation site, reduces PP1 inhibition |
| c.205G>A (p.Glu69Lys) | Missense | <0.01% | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
Thr34Met mutation reduces ability to inhibit PP1, impairing dopamine signaling.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Not described for PPP1R1A.
View complete mutation data：
Gene Ontology (GO)
| • protein phosphatase inhibitor activity (GO:0004864) | • protein binding (GO:0005515) |
| • cytoplasm (GO:0005737) | • plasma membrane (GO:0005886) |
| • chemical synaptic transmission (GO:0007268) |
Pathways
• Dopamine-DARPP32 feedback in cAMP signaling (Reactome: R-HSA-389977)
• Glutamate signaling pathway (KEGG: hsa04724)
Protein Summary
DARPP-32 is a 32 kDa protein that acts as a molecular switch integrating dopaminergic and glutamatergic signals. Upon phosphorylation at Thr34 by cAMP-dependent PKA, it becomes a potent inhibitor of PP1, thereby amplifying downstream signaling. It is critical for synaptic plasticity, motor control, and reward pathways.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPP1R1A Knockout HEK293 Cell Line | EDJ-KQ5516 | Human | 5502 | Details Get a Quote |
| PPP1R1A Knockout HCT 116 Cell Line | EDJ-KQ28763 | Human | 5502 | Details Get a Quote |
| PPP1R1A Knockout HeLa Cell Line | EDJ-KQ54192 | Human | 5502 | Details Get a Quote |
| PPP1R1A Knockout A-549 Cell Line | EDJ-KQ62686 | Human | 5502 | Details Get a Quote |
