PTPRS (Protein Tyrosine Phosphatase Receptor Type S): A Key Regulator in Neural Development and Cancer
Explore the PTPRS gene, its protein product, genomic context, expression patterns, associated diseases, and mutation landscape. This comprehensive guide covers essential information for researchers and clinicians.
Gene Information Card
| Symbol | PTPRS |
|---|---|
| Full Name | Protein Tyrosine Phosphatase Receptor Type S |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 5802 ncbi.nlm.nih.gov/gene/5802 |
| Ensembl ID | ENSG00000105426 |
| UniProt ID | Q13332 |
| OMIM ID | 607352 |
| HGNC ID | 9681 |
| Aliases | PTPsigma, PTP-S, R-PTP-S, HPTP sigma |
Description
The PTPRS gene encodes protein tyrosine phosphatase receptor type S (PTPRS), also known as PTP sigma. This protein is a member of the receptor-type protein tyrosine phosphatase (RPTP) family. PTPRS is a type I transmembrane protein with extracellular fibronectin type III and immunoglobulin-like domains, and two intracellular tyrosine phosphatase domains. It plays a critical role in various cellular processes, including neural development, axon guidance, cell adhesion, and immune regulation. PTPRS is widely expressed, particularly in the nervous system, and has been implicated in several diseases, notably cancer and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | PTPRS can act as a tumor suppressor. Loss of function or reduced expression can lead to increased cell proliferation, survival, and migration. It regulates pathways like the EGFR and Wnt signaling pathways. | Multiple studies show reduced PTPRS expression in various cancers (e.g., colorectal, lung, breast, glioblastoma). Somatic mutations and promoter hypermethylation have been identified in tumor samples (COSMIC, ClinVar). |
| Neurodevelopmental disorders | PTPRS is crucial for neuronal development and axon guidance. Mutations may disrupt these processes, contributing to conditions like intellectual disability and autism spectrum disorder. | Rare variants and copy number variations in PTPRS have been found in patients with neurodevelopmental phenotypes (ClinVar, literature). |
| Obesity and Metabolic Syndrome | PTPRS is involved in the regulation of body weight and energy metabolism, potentially through its role in the hypothalamus. | Genome-wide association studies (GWAS) have linked PTPRS variants to body mass index (BMI) and obesity risk (literature). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 17.2 | High |
| Adrenal Gland | 8.5 | Medium |
| Lung | 6.1 | Medium |
| Kidney | 5.8 | Medium |
| Liver | 2.3 | Low |
| Heart | 1.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (Neuroblastoma) | 15.4 | High expression, consistent with neural origin. |
| A549 (Lung Carcinoma) | 7.8 | Moderate expression. |
| MCF7 (Breast Carcinoma) | 4.2 | Low to moderate expression. |
| HepG2 (Hepatocellular Carcinoma) | 1.5 | Low expression. |
| K562 (Leukemia) | 0.8 | Very low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Ter) | Nonsense | Rare (<0.1%) | Introduces a premature stop codon, leading to a truncated, likely non-functional protein. Associated with loss of tumor suppressor function. |
| c.456_459del (p.Glu153fs) | Frameshift | Rare (<0.1%) | Causes a frameshift in the extracellular domain, likely leading to protein misfolding and degradation. |
| c.789A>G (p.Ile263Met) | Missense | Rare (<0.1%) | Substitution in the extracellular domain. Predicted to be damaging by in silico tools; functional impact is under investigation. |
| c.2345C>T (p.Thr782Met) | Missense | Rare (<0.1%) | Located in the intracellular phosphatase domain. May affect catalytic activity. |
Mutation functional classification
Loss of Function (LOF)
The most common mechanism in cancer. Nonsense, frameshift, and splice-site mutations, along with promoter hypermethylation, lead to reduced or absent PTPRS protein, removing its tumor-suppressive effects.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented for PTPRS. The gene is primarily considered a tumor suppressor, so activating mutations are not a typical feature.
Dominant Negative (DN)
Some missense mutations in the extracellular or intracellular domains could potentially exert a dominant-negative effect by dimerizing with wild-type PTPRS and inhibiting its function, though this is not a well-established mechanism for this gene.
View complete mutation data：
Gene Ontology (GO)
| • protein tyrosine phosphatase activity | • transmembrane receptor protein tyrosine phosphatase activity |
| • protein binding | • heparin binding |
| • signal transduction | • cell adhesion |
| • axon guidance | • nervous system development |
| • peptidyl-tyrosine dephosphorylation | • plasma membrane |
| • integral component of plasma membrane |
Pathways
• Axon guidance
• Signaling by Receptor Tyrosine Kinases
• EGFR tyrosine kinase inhibitor resistance
• Wnt signaling pathway
• MAPK signaling pathway
Protein Summary
The PTPRS protein is a ~200 kDa type I transmembrane receptor. Its extracellular region contains three immunoglobulin-like domains and eight fibronectin type III repeats, which are involved in cell-cell and cell-matrix interactions. The intracellular region contains two tandem protein tyrosine phosphatase (PTP) domains. The membrane-proximal domain (D1) is catalytically active, while the membrane-distal domain (D2) is thought to be regulatory. PTPRS functions as a signaling molecule that dephosphorylates specific tyrosine residues on target proteins, thereby modulating intracellular signaling cascades. It plays a critical role in neuronal development, particularly in axon guidance and synapse formation, and acts as a tumor suppressor in various tissues by negatively regulating cell growth and survival pathways.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PTPRS Knockout HEK293 Cell Line | EDJ-KQ3050 | Human | 5802 | Details Get a Quote |
| PTPRS Knockout A-549 Cell Line | EDJ-KQ24298 | Human | 5802 | Details Get a Quote |
| PTPRS Knockout HCT 116 Cell Line | EDJ-KQ24299 | Human | 5802 | Details Get a Quote |
| PTPRS Knockout HeLa Cell Line | EDJ-KQ24300 | Human | 5802 | Details Get a Quote |
