PTPN5
Protein Tyrosine Phosphatase, Non-Receptor Type 5
Gene Information Card
| Symbol | PTPN5 |
|---|---|
| Full Name | Protein Tyrosine Phosphatase, Non-Receptor Type 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.1 |
| NCBI Gene ID | 84867 ncbi.nlm.nih.gov/gene/84867 |
| Ensembl ID | ENSG00000149273 |
| UniProt ID | P54829 |
| OMIM ID | 176979 |
| HGNC ID | 9659 |
| Aliases | STEP, STEP61, STEP46, PTPSTEP |
Description
PTPN5 encodes a brain-specific protein tyrosine phosphatase known as STEP (striatal-enriched phosphatase). It is involved in the regulation of synaptic plasticity by dephosphorylating key neuronal substrates such as NMDA and AMPA receptors, ERK1/2, and Fyn. Alternative splicing produces two major isoforms: STEP61 (membrane-associated) and STEP46 (cytosolic). Dysregulation of PTPN5 is implicated in neuropsychiatric and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | Increased STEP61 levels lead to enhanced dephosphorylation of GluN2B and GluA2, promoting internalization of NMDA and AMPA receptors and contributing to synaptic loss. | ClinVar, PMID: 20628056 |
| Huntington disease | STEP61 is upregulated in striatal neurons; aberrant dephosphorylation of ERK1/2 and Fyn impairs synaptic signaling and survival. | PMID: 21228169 |
| Schizophrenia | Reduced STEP61 expression alters NMDA receptor trafficking and glutamatergic signaling, linked to cognitive deficits. | PMID: 20064376 |
| Parkinson disease | Dysregulation of STEP in dopaminergic neurons affects ERK signaling and synaptic plasticity. | PMID: 25319628 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 22.5 | High |
| Brain (hippocampus) | 18.3 | High |
| Brain (striatum) | 35.1 | High |
| Brain (cerebellum) | 12.7 | Medium |
| Testis | 1.2 | Low |
| Other tissues | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.4 | Endogenous expression |
| SK-N-SH (neuroblastoma) | 12.8 | Endogenous expression |
| HEK293 (embryonic kidney) | 0.3 | Very low/transient |
| U-87 MG (glioblastoma) | 8.1 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.01% | Unknown functional effect; rare population variant |
| c.487G>A (p.Gly163Arg) | Missense | <0.01% | Predicted damaging; loss of phosphatase activity |
| c.1120C>T (p.Arg374Trp) | Missense | <0.01% | Unknown; located in catalytic domain |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the catalytic domain (e.g., p.Gly163Arg) reduce phosphatase activity, impairing dephosphorylation of substrates like ERK1/2 and GluN2B.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in PTPN5.
Dominant Negative (DN)
No dominant-negative mutations described for PTPN5.
View complete mutation data：
Gene Ontology (GO)
| • protein tyrosine phosphatase activity (GO:0004725) | • cytoplasm (GO:0005737) |
| • plasma membrane (GO:0005886) | • dephosphorylation (GO:0016311) |
| • synapse (GO:0045202) | • excitatory postsynaptic potential (GO:0060076) |
| • cation channel complex (GO:0098655) |
Pathways
• NMDA receptor signaling (Reactome R-HSA-438066)
• MAPK/ERK signaling (Reactome R-HSA-5673001)
• Long-term depression (KEGG hsa04730)
• Glutamatergic synapse (KEGG hsa04724)
Protein Summary
PTPN5 (STEP) is a brain-enriched non-receptor protein tyrosine phosphatase that negatively regulates synaptic plasticity by dephosphorylating key signaling proteins including NMDA and AMPA receptor subunits, ERK1/2, and Fyn. It exists as two major isoforms: STEP61 (membrane-bound) and STEP46 (cytosolic). STEP61 is localized to postsynaptic densities and endosomes, while STEP46 is predominantly cytosolic. Dysregulation of STEP contributes to cognitive deficits in Alzheimer disease, Huntington disease, and schizophrenia. Therapeutic strategies targeting STEP inhibition are under investigation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PTPN5 Knockout HEK293 Cell Line | EDJ-KQ740 | Human | 84867 | Details Get a Quote |
| PTPN5 Knockout HeLa Cell Line | EDJ-KQ57670 | Human | 84867 | Details Get a Quote |
| PTPN5 Knockout A-549 Cell Line | EDJ-KQ66170 | Human | 84867 | Details Get a Quote |
| PTPN5 Knockout HCT 116 Cell Line | EDJ-KQ74596 | Human | 84867 | Details Get a Quote |
