PHLPP2
PH Domain and Leucine Rich Repeat Protein Phosphatase 2
Gene Information Card
| Symbol | PHLPP2 |
|---|---|
| Full Name | PH domain and leucine rich repeat protein phosphatase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 16q22.2 |
| NCBI Gene ID | 23035 ncbi.nlm.nih.gov/gene/23035 |
| Ensembl ID | ENSG00000140105 |
| UniProt ID | Q6ZVD8 |
| OMIM ID | 611066 |
| HGNC ID | 20611 |
| Aliases | PHLPP2, PHLPP-like, PHLPPL, SCOP2 |
Description
PHLPP2 (PH domain and leucine rich repeat protein phosphatase 2) is a protein-coding gene that encodes a member of the PHLPP family of serine/threonine phosphatases. The protein contains a PH domain, leucine-rich repeats, and a PP2C-like phosphatase domain. It functions as a tumor suppressor by dephosphorylating and inactivating AKT and other AGC kinases, thereby regulating cell survival, proliferation, and apoptosis. PHLPP2 is widely expressed in human tissues and is implicated in various cancers and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Loss of PHLPP2 expression leads to increased AKT phosphorylation and cell proliferation | PMID: 20010870 |
| Breast cancer | Reduced PHLPP2 levels correlate with poor prognosis and enhanced AKT signaling | PMID: 20534588 |
| Prostate cancer | PHLPP2 downregulation promotes tumor growth and metastasis | PMID: 21804531 |
| Glioblastoma | PHLPP2 inactivation contributes to AKT hyperactivation and resistance to therapy | PMID: 23103861 |
| Type 2 diabetes | PHLPP2 regulates insulin signaling via AKT dephosphorylation | PMID: 20813262 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.7 | Low |
| Kidney | 10.1 | Medium |
| Lung | 9.4 | Low |
| Colon | 11.2 | Medium |
| Breast | 7.8 | Low |
| Prostate | 9.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 12.8 | Medium expression |
| MCF7 | 10.5 | Medium expression |
| A549 | 9.1 | Low expression |
| HCT116 | 11.7 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | 0.02% | Loss of function |
| c.567G>A (p.Trp189*) | Nonsense | 0.01% | Loss of function |
| c.890A>G (p.Glu297Gly) | Missense | 0.05% | Unknown |
| c.1456_1457del (p.Leu486fs) | Frameshift | 0.01% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt the phosphatase domain lead to loss of AKT dephosphorylation activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported.
Dominant Negative (DN)
No dominant-negative mutations have been described.
View complete mutation data：
Gene Ontology (GO)
Pathways
• PI3K/AKT signaling pathway
• Insulin signaling pathway
• mTOR signaling pathway
• Apoptosis
Protein Summary
PHLPP2 is a 1205-amino acid protein with a molecular weight of approximately 134 kDa. It contains an N-terminal PH domain, a series of leucine-rich repeats (LRRs), and a C-terminal PP2C-like phosphatase domain. The PH domain targets the protein to the plasma membrane, where it dephosphorylates AKT at Ser473, leading to AKT inactivation. PHLPP2 also dephosphorylates other AGC kinases such as PKC and S6K1. The protein is regulated by ubiquitin-mediated degradation and is frequently downregulated in cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PHLPP2 Knockout HEK293 Cell Line | EDJ-KQ842 | Human | 23035 | Details Get a Quote |
| PHLPP2 Knockout A-549 Cell Line | EDJ-KQ19630 | Human | 23035 | Details Get a Quote |
| PHLPP2 Knockout HCT 116 Cell Line | EDJ-KQ19631 | Human | 23035 | Details Get a Quote |
| PHLPP2 Knockout HeLa Cell Line | EDJ-KQ19632 | Human | 23035 | Details Get a Quote |
