phosphatase and tensin homolog | Lipid phosphate phosphatases | IUPHAR/BPS Guide to PHARMACOLOGY

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phosphatase and tensin homolog

target has curated data in GtoImmuPdb

Target id: 2497

Nomenclature: phosphatase and tensin homolog

Abbreviated Name: PTEN

Family: Lipid phosphate phosphatases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 403 10q23.3 PTEN phosphatase and tensin homolog
Mouse - 403 19 C1 Pten phosphatase and tensin homolog
Rat - 403 1q41-q43 Pten phosphatase and tensin homolog
Previous and Unofficial Names
BZS | MMAC1 | mutated in multiple advanced cancers 1 | TEP1
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.1.3.16
EC Number: 3.1.3.48
EC Number: 3.1.3.67
Substrates and Reaction Kinetics
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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
P6949 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
GO Annotations:  Associated to 1 GO processes
GO:1904668 positive regulation of ubiquitin protein ligase activity IDA
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0050765 negative regulation of phagocytosis IEA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002902 regulation of B cell apoptotic process IEA
Phenotypes, Alleles and Disease Models Mouse data from MGI

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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

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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 12/11/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2497.