PTPN1: Protein Tyrosine Phosphatase Non-Receptor Type 1
A key regulator of insulin and leptin signaling, implicated in metabolic disorders and cancer.
Gene Information Card
| Symbol | PTPN1 |
|---|---|
| Full Name | Protein Tyrosine Phosphatase Non-Receptor Type 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 20q13.13 |
| NCBI Gene ID | 5770 ncbi.nlm.nih.gov/gene/5770 |
| Ensembl ID | ENSG00000196396 |
| UniProt ID | P18031 |
| OMIM ID | 176885 |
| HGNC ID | 9642 |
| Aliases | PTP1B, PTP-1B |
Description
PTPN1 encodes protein tyrosine phosphatase 1B (PTP1B), a non-receptor phosphatase that negatively regulates insulin and leptin signaling by dephosphorylating the insulin receptor and JAK2. It is a therapeutic target for type 2 diabetes and obesity. PTPN1 also plays roles in cell growth, differentiation, and oncogenic signaling, with alterations linked to breast, colorectal, and prostate cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 diabetes mellitus | PTP1B overexpression reduces insulin receptor phosphorylation, impairing glucose uptake. | NCBI Gene, OMIM |
| Obesity | PTP1B dephosphorylates JAK2, attenuating leptin signaling and promoting leptin resistance. | OMIM, UniProt |
| Breast cancer | PTPN1 amplification/overexpression enhances HER2 signaling; loss-of-function may suppress tumor growth. | COSMIC, NCBI Gene |
| Colorectal cancer | Somatic mutations and copy number gains in PTPN1 are recurrent. | COSMIC |
| Metabolic syndrome | Combined insulin and leptin resistance due to PTP1B dysregulation. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Adipose tissue | 9.8 | Medium |
| Skeletal muscle | 7.3 | Low |
| Brain | 5.1 | Low |
| Pancreas | 4.6 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.2 | Hepatocellular carcinoma line |
| MCF7 | 11.0 | Breast cancer line |
| HT-29 | 9.5 | Colorectal adenocarcinoma line |
| HEK 293 | 8.1 | Embryonic kidney line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.981C>T (p.Arg327*) | Nonsense | <0.1% | Loss of function; truncation of catalytic domain |
| c.1040G>A (p.Arg347His) | Missense | <0.1% | Reduced phosphatase activity |
| c.1123C>T (p.Arg375Trp) | Missense | <0.1% | Impaired substrate binding |
| Amplification (20q13.13) | Copy number gain | ~5% in breast cancer | Increased PTP1B expression; oncogenic |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg327*, p.Arg347His) reduce or abolish phosphatase activity, potentially enhancing insulin sensitivity but also affecting cell growth regulation.
Gain of Function (GOF)
Gene amplification and overexpression in breast cancer lead to increased PTP1B activity, promoting HER2 signaling and tumor progression.
Dominant Negative (DN)
Not well documented; some missense variants may interfere with substrate binding but no clear dominant-negative effect reported.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004725 – protein tyrosine phosphatase activity | • GO:0005737 – cytoplasm |
| • GO:0005886 – plasma membrane | • GO:0008286 – insulin receptor signaling pathway |
| • GO:0019901 – protein kinase binding | • GO:0035335 – peptidyl-tyrosine dephosphorylation |
Pathways
• Insulin signaling pathway (Reactome R-HSA-74752)
• Leptin signaling pathway (Reactome R-HSA-2586552)
• EGFR/ERBB2 signaling (Reactome R-HSA-177929)
• JAK-STAT signaling (Reactome R-HSA-913531)
Protein Summary
PTP1B is a 435-amino acid protein with a conserved N-terminal catalytic domain and a C-terminal endoplasmic reticulum targeting sequence. It dephosphorylates tyrosine residues on activated receptor tyrosine kinases (e.g., insulin receptor, EGFR, HER2) and JAK kinases. PTP1B is a validated drug target for metabolic disease; inhibitors are in clinical development. In cancer, its role is context-dependent: it can act as a tumor suppressor or oncogene depending on the cellular environment.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PTPN18 Knockout HEK293 Cell Line | EDJ-KQ1384 | Human | 26469 | Details Get a Quote |
| PTPN1 Knockout HEK293 Cell Line | EDJ-KQ2304 | Human | 5770 | Details Get a Quote |
| PTPN12 Knockout HEK293 Cell Line | EDJ-KQ2400 | Human | 5782 | Details Get a Quote |
| PTPN13 Knockout HEK293 Cell Line | EDJ-KQ2952 | Human | 5783 | Details Get a Quote |
| PTPN14 Knockout HEK293 Cell Line | EDJ-KQ4834 | Human | 5784 | Details Get a Quote |
| PTPN18 Knockout A-549 Cell Line | EDJ-KQ22187 | Human | 26469 | Details Get a Quote |
| PTPN18 Knockout HCT 116 Cell Line | EDJ-KQ22189 | Human | 26469 | Details Get a Quote |
| PTPN18 Knockout HeLa Cell Line | EDJ-KQ22190 | Human | 26469 | Details Get a Quote |
| PTPN13 Knockout A-549 Cell Line | EDJ-KQ24087 | Human | 5783 | Details Get a Quote |
| PTPN13 Knockout HCT 116 Cell Line | EDJ-KQ24088 | Human | 5783 | Details Get a Quote |
| PTPN13 Knockout HeLa Cell Line | EDJ-KQ24089 | Human | 5783 | Details Get a Quote |
| PTPN1 Knockout HCT 116 Cell Line | EDJ-KQ21351 | Human | 5770 | Details Get a Quote |
| PTPN1 Knockout A-549 Cell Line | EDJ-KQ22680 | Human | 5770 | Details Get a Quote |
| PTPN1 Knockout HeLa Cell Line | EDJ-KQ22682 | Human | 5770 | Details Get a Quote |
| PTPN12 Knockout A-549 Cell Line | EDJ-KQ24260 | Human | 5782 | Details Get a Quote |
Displaying Records 1 To 15 Of 24 Records
