PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten)

1999-07-01   Michel Longy 

Unite de Genetique Oncologique, Institut Bergonie, 180, rue de Saint-Genes, 33076 Bordeaux, France

Identity

HGNC
LOCATION
10q23.31
IMAGE
Atlas Image
LEGEND
PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten) Hybridization with Kreatech ON PTEN (10q23)/SE 10 probe (Kreatech, Leica Biosystems Inc., US) showing PTEN on 10q23.31 (red signals) - Courtesy Adriana Zamecnikova.
LOCUSID
ALIAS
10q23del,BZS,CWS1,DEC,GLM2,MHAM,MMAC1,PTEN1,PTENbeta,TEP1
FUSION GENES

DNA/RNA

Description

9 exons, all coding; exon 1 has an unusually long 5 untranslated GC-rich region; exon 5 codes for the phosphatase core motif

Transcription

2 major detected transcripts; respectively 2 and 5 kb; open reading frame : 1209 bp

Proteins

Description

403 aminoacids, 47 kDa; N-terminal phosphatase domain (from a.a. 1 to 185) with the catalytic core motif between; a.a. 123-131 encoded by exon 5; C-terminal PDZ binding domain

Localisation

cytoplasmic localization (immunohistochemistry)

Function

phosphatase activity; substrate : phosphatidylinositol 3,4,5-tri phosphate (PIP3); PTEN appears as a negative regulator of the PI3K/AKT signaling pathway; It is unclear if PTEN is able to dephosphorylate a protein substrate in vivo; tumor suppressive function: biallelic inactivation is observed in several tumor-types and inactivating germline mutations are responsible for a cancer prone syndrome, the Cowden disease; anti-invasive and anti-proliferative effects were documented in several cell lines

Mutations

Germinal

germline mutations have been documented in Cowden disease and in Bannayan, Riley, Ruvalcaba phenotype (see below); they are observed along the various exons of the gene except the 9th (never described) and the 1st (very few reports); a mutational hot spot is observed in exon 5 in relation with the catalytic core motif; in the great majority of the cases, inactivating mutations are observed, either by protein truncation, or by misense mutation within the phosphatase domain

Somatic

mutations are observed in several tumor type; they lead to a biallelic inactivation of the gene either by homozygous deletion, or by a combination of point mutation and a large deletion of the second allele

Implicated in

Entity name
Cowden disease and Bannayan, Riley, Ruvalcaba phenotype
Disease
Cowden disease is also known as multiple hamartoma syndrome, a cancer prone condition with autosomal dominant pattern of inheritance and high susceptibility to breast carcinoma and in a less extent to thyroid carcinoma; Bannayan, Ryley, Ruvalcaba syndrome correspond to the pediatric contrepart of Cowden disease with phenotypic overlap between the 2 syndromes (macrocephaly, intestinal polyps, lipomas, genital pigmented macules)
Entity name
sporadic malignant tumors
Disease
somatic mutations were observed mainly in glioblastoma and in endometrial carcinoma, about 30% of these two kinds of tumors showing point mutations; only a few mutations were reported in prostate carcinoma, malignant melanoma, non Hodgkin lymphomas, breast carcinoma

Bibliography

Pubmed IDLast YearTitleAuthors
90729741997PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.Li J et al
95936641998The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate.Maehama T et al
94670111998Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.Marsh DJ et al
93999171997PTEN: sometimes taking it off can be better than putting it on.Myers MP et al
90903791997Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers.Steck PA et al

Other Information

Locus ID:

NCBI: 5728
MIM: 601728
HGNC: 9588
Ensembl: ENSG00000171862

Variants:

dbSNP: 5728
ClinVar: 5728
TCGA: ENSG00000171862
COSMIC: PTEN

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000171862ENST00000371953P60484
ENSG00000171862ENST00000371953F6KD01
ENSG00000171862ENST00000472832A0A087X033

Expression (GTEx)

0
10
20
30
40
50
60
70

Pathways

PathwaySourceExternal ID
Inositol phosphate metabolismKEGGko00562
Phosphatidylinositol signaling systemKEGGko04070
p53 signaling pathwayKEGGko04115
Autophagy - animalKEGGko04140
mTOR signaling pathwayKEGGko04150
Focal adhesionKEGGko04510
Endometrial cancerKEGGko05213
GliomaKEGGko05214
Prostate cancerKEGGko05215
MelanomaKEGGko05218
Small cell lung cancerKEGGko05222
Inositol phosphate metabolismKEGGhsa00562
Phosphatidylinositol signaling systemKEGGhsa04070
p53 signaling pathwayKEGGhsa04115
Autophagy - animalKEGGhsa04140
mTOR signaling pathwayKEGGhsa04150
Focal adhesionKEGGhsa04510
Pathways in cancerKEGGhsa05200
Endometrial cancerKEGGhsa05213
GliomaKEGGhsa05214
Prostate cancerKEGGhsa05215
MelanomaKEGGhsa05218
Small cell lung cancerKEGGhsa05222
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Hepatitis BKEGGhsa05161
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
FoxO signaling pathwayKEGGhsa04068
Central carbon metabolism in cancerKEGGhsa05230
Central carbon metabolism in cancerKEGGko05230
Sphingolipid signaling pathwayKEGGhsa04071
Sphingolipid signaling pathwayKEGGko04071
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
TCR signalingREACTOMER-HSA-202403
Downstream TCR signalingREACTOMER-HSA-202424
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
PIP3 activates AKT signalingREACTOMER-HSA-1257604
Negative regulation of the PI3K/AKT networkREACTOMER-HSA-199418
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
Role of LAT2/NTAL/LAB on calcium mobilizationREACTOMER-HSA-2730905
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GAB1 signalosomeREACTOMER-HSA-180292
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
PI3K/AKT activationREACTOMER-HSA-198203
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by SCF-KITREACTOMER-HSA-1433557
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
TP53 Regulates Metabolic GenesREACTOMER-HSA-5628897
MetabolismREACTOMER-HSA-1430728
Inositol phosphate metabolismREACTOMER-HSA-1483249
Synthesis of IP3 and IP4 in the cytosolREACTOMER-HSA-1855204
Metabolism of lipids and lipoproteinsREACTOMER-HSA-556833
Phospholipid metabolismREACTOMER-HSA-1483257
PI MetabolismREACTOMER-HSA-1483255
Synthesis of PIPs at the plasma membraneREACTOMER-HSA-1660499
Insulin resistanceKEGGhsa04931
EGFR tyrosine kinase inhibitor resistanceKEGGko01521
EGFR tyrosine kinase inhibitor resistanceKEGGhsa01521
DeubiquitinationREACTOMER-HSA-5688426
Ub-specific processing proteasesREACTOMER-HSA-5689880
Ovarian tumor domain proteasesREACTOMER-HSA-5689896
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA128406956fluorouracilChemicalClinicalAnnotationassociatedPD
PA33312PIK3R1GeneMultilinkAnnotationassociated26807692
PA443622Carcinoma, Non-Small-Cell LungDiseaseClinicalAnnotationassociatedPD
PA444342Hamartoma Syndrome, MultipleDiseaseDataAnnotation, Literature, MultilinkAnnotationassociated23788249
PA445058Neoplasm MetastasisDiseaseClinicalAnnotationassociatedPD
PA445425Prostatic NeoplasmsDiseaseMultilinkAnnotationassociated24491799
PA448771capecitabineChemicalClinicalAnnotationassociatedPD
PA448803carboplatinChemicalClinicalAnnotationassociatedPD
PA449014cisplatinChemicalClinicalAnnotationassociatedPD

References

Pubmed IDYearTitleCitations
176811832007MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer.931
224734682012The functions and regulation of the PTEN tumour suppressor.685
179365632007A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer.516
179365632007A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer.516
212523152011DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.498
181995362008MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN.424
215758592011Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer.424
186768302008An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer.396
220000132011Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs.380
172182622007Essential role for nuclear PTEN in maintaining chromosomal integrity.350

Citation

Michel Longy

PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten)

Atlas Genet Cytogenet Oncol Haematol. 1999-07-01

Online version: http://atlasgeneticsoncology.org/gene/158/pten