Top ▲

phosphatase and tensin homolog

Click here for help

Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2497

Nomenclature: phosphatase and tensin homolog

Abbreviated Name: PTEN

Family: Lipid phosphate phosphatases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 403 10q23.31 PTEN phosphatase and tensin homolog
Mouse - 403 19 28.14 cM Pten phosphatase and tensin homolog
Rat - 403 1q41-q43 Pten phosphatase and tensin homolog
Previous and Unofficial Names Click here for help
BZS | MMAC1 | mutated in multiple advanced cancers 1 | TEP1
Database Links Click here for help
Alphafold
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 3.1.3.16
EC Number: 3.1.3.48
EC Number: 3.1.3.67
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
phosphatidylinositol (3,4,5)-trisphosphate Hs - -

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
P6949 Small molecule or natural product Hs Inhibition 5.1 pIC50 1
pIC50 5.1 (IC50 8.87x10-6 M) [1]
Immunopharmacology Comments
Accumulating evidence suggests that loss-of-function mutations or deletion of PTEN is an immune evasion mechanism exploited by tumour cells [5], and that disrupted PTEN activity may have implications for resistance to T cell-mediated immunotherapy (checkpoint blockade) [2,4].
Immuno Process Associations
Immuno Process:  Cellular signalling
Immuno Process:  Inflammation
Immuno Process:  B cell (activation)
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Pgr+|Pgrtm2(cre)Lyd|Ptentm1Hwu Pgrtm2(cre)Lyd/Pgr+,Ptentm1Hwu/Ptentm1Hwu
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
MGI:109583  MGI:97567  MP:0004868 endometrial carcinoma PMID: 18632614 
Pgr+|Pgrtm2(cre)Lyd|Ptentm1Hwu|Trp53tm1Brn Pgrtm2(cre)Lyd/Pgr+,Ptentm1Hwu/Ptentm1Hwu,Trp53tm1Brn/Trp53tm1Brn
involves: 129 * C57BL/6
MGI:109583  MGI:97567  MGI:98834  MP:0004868 endometrial carcinoma PMID: 18632614 
Pgr+|Pgrtm2(cre)Lyd|Ptentm1Hwu Pgrtm2(cre)Lyd/Pgr+,Ptentm1Hwu/Ptentm1Hwu
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
MGI:109583  MGI:97567  MP:0009092 endometrium hyperplasia PMID: 18632614 
Pgr+|Pgrtm2(cre)Lyd|Ptentm1Hwu|Trp53tm1Brn Pgrtm2(cre)Lyd/Pgr+,Ptentm1Hwu/Ptentm1Hwu,Trp53tm1Brn/Trp53tm1Brn
involves: 129 * C57BL/6
MGI:109583  MGI:97567  MGI:98834  MP:0009092 endometrium hyperplasia PMID: 18632614 
Pgr+|Pgrtm2(cre)Lyd|Ptentm1Hwu|Trp53tm1Brn Pgrtm2(cre)Lyd/Pgr+,Ptentm1Hwu/Ptentm1Hwu,Trp53tm1Brn/Trp53tm1Brn
involves: 129 * C57BL/6
MGI:109583  MGI:97567  MGI:98834  MP:0004906 enlarged uterus PMID: 18632614 
Pgr+|Pgrtm2(cre)Lyd|Ptentm1Hwu Pgrtm2(cre)Lyd/Pgr+,Ptentm1Hwu/Ptentm1Hwu
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
MGI:109583  MGI:97567  MP:0002083 premature death PMID: 18632614 
Pgr+|Pgrtm2(cre)Lyd|Ptentm1Hwu|Trp53tm1Brn Pgrtm2(cre)Lyd/Pgr+,Ptentm1Hwu/Ptentm1Hwu,Trp53tm1Brn/Trp53tm1Brn
involves: 129 * C57BL/6
MGI:109583  MGI:97567  MGI:98834  MP:0002083 premature death PMID: 18632614 
General Comments
PTEN's phosphatase activity dephosphorylates phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5)P3 or PIP3) to PIP2 (which leads to inhibition of the AKT signaling pathway), and it also appears to have some protein phosphatase activity. PTEN acts as a tumour suppressor. Inactivation of PTEN expression (by mutation or deletion) is one of the most common oncogenic pathways identified in human cancers. PTEN mutations have also been identified in non-cancerous neoplasia (e.g. hamartomas) [3,6-7].

References

Show »

1. Mak LH, Knott J, Scott KA, Scott C, Whyte GF, Ye Y, Mann DJ, Ces O, Stivers J, Woscholski R. (2012) Arylstibonic acids are potent and isoform-selective inhibitors of Cdc25a and Cdc25b phosphatases. Bioorg Med Chem, 20 (14): 4371-6. [PMID:22705189]

2. Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, Xu C, McKenzie JA, Zhang C, Liang X et al.. (2016) Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy. Cancer Discov, 6 (2): 202-16. [PMID:26645196]

3. Pilarski R, Eng C. (2004) Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome. J Med Genet, 41 (5): 323-6. [PMID:15121767]

4. Roh W, Chen PL, Reuben A, Spencer CN, Prieto PA, Miller JP, Gopalakrishnan V, Wang F, Cooper ZA, Reddy SM et al.. (2017) Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance. Sci Transl Med, 9 (379). [PMID:28251903]

5. Spranger S, Gajewski TF. (2018) Impact of oncogenic pathways on evasion of antitumour immune responses. Nat Rev Cancer, 18 (3): 139-147. [PMID:29326431]

6. Uemura S, Matsubayashi H, Kiyozumi Y, Uesaka K, Yamamoto Y, Sasaki K, Abe M, Urakami K, Kusuhara M, Yamaguchi K. (2018) Pancreatic adenocarcinoma with a germline PTEN p.Arg234Gln mutation. Fam Cancer, 17 (2): 255-259. [PMID:28755079]

7. Yakubov E, Ghoochani A, Buslei R, Buchfelder M, Eyüpoglu IY, Savaskan N. (2016) Hidden association of Cowden syndrome, PTEN mutation and meningioma frequency. Oncoscience, 3 (5-6): 149-55. [PMID:27489861]

How to cite this page

Lipid phosphate phosphatases: phosphatase and tensin homolog. Last modified on 10/07/2018. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2497.