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PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten)

Identity

Other namesMMAC1 (Mutated in Multiple Advanced Cancer 1)
TEP 1 (TGFb regulated and Epithelial cell enriched Phosphatase 1)
HGNC (Hugo) PTEN
LocusID (NCBI) 5728
Location 10q23.31
Location_base_pair Starts at 89623195 and ends at 89728532 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order between D10S1765 and D10S541

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

Protein

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 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 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
  

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004 rhabID5004 blad5001
bladID5001 colon5006 colonID5006

External links

Nomenclature
HGNC (Hugo)PTEN   9588
Cards
AtlasPTENID158
Entrez_Gene (NCBI)PTEN  5728  phosphatase and tensin homolog
GeneCards (Weizmann)PTEN
Ensembl (Hinxton) [Gene_View]  chr10:89623195-89728532 [Contig_View]  PTEN [Vega]
cBioPortalPTEN
AceView (NCBI)PTEN
Genatlas (Paris)PTEN
WikiGenes5728
SOURCE (Princeton)NM_000314
Genomic and cartography
GoldenPath (UCSC)PTEN  -  10q23.31   chr10:89623195-89728532 +  10q23   [Description]    (hg19-Feb_2009)
EnsemblPTEN - 10q23 [CytoView]
Mapping of homologs : NCBIPTEN [Mapview]
OMIM153480   155600   158350   176807   188470   275355   276950   601728   605309   607174   608089   613028   
Gene and transcription
Genbank (Entrez)AA017584 AI825848 AK021619 AK024986 AK124525
RefSeq transcript (Entrez)NM_000314
RefSeq genomic (Entrez)AC_000142 NC_000010 NC_018921 NG_007466 NT_030059 NW_001838005 NW_004929376
Consensus coding sequences : CCDS (NCBI)PTEN
Cluster EST : UnigeneHs.500466 [ NCBI ]
CGAP (NCI)Hs.500466
Alternative Splicing : Fast-db (Paris)GSHG0003534
Gene ExpressionPTEN [ NCBI-GEO ]     PTEN [ SEEK ]   PTEN [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP60484 (Uniprot)
NextProtP60484  [Medical]
With graphics : InterProP60484
Splice isoforms : SwissVarP60484 (Swissvar)
Catalytic activity : Enzyme3.1.3.16 [ Enzyme-Expasy ]   3.1.3.163.1.3.16 [ IntEnz-EBI ]   3.1.3.16 [ BRENDA ]   3.1.3.16 [ KEGG ]   
Domaine pattern : Prosite (Expaxy)C2_TENSIN (PS51182)    PPASE_TENSIN (PS51181)   
Domains : Interpro (EBI)Bifunc_PIno_P3_Pase/Pase_PTEN [organisation]   C2_dom [organisation]   Dual-sp_phosphatase_cat-dom [organisation]   Prot-tyrosine_phosphatase-like [organisation]   Tensin_C2-dom [organisation]   Tensin_lipid_phosphatase_dom [organisation]   Tyr_Pase_AS [organisation]  
Related proteins : CluSTrP60484
Domain families : Pfam (Sanger)DSPc (PF00782)    PTEN_C2 (PF10409)   
Domain families : Pfam (NCBI)pfam00782    pfam10409   
DMDM Disease mutations5728
Blocks (Seattle)P60484
PDB (SRS)1D5R    2KYL   
PDB (PDBSum)1D5R    2KYL   
PDB (IMB)1D5R    2KYL   
PDB (RSDB)1D5R    2KYL   
Peptide AtlasP60484
HPRD03431
Protein Interaction databases
DIP (DOE-UCLA)P60484
IntAct (EBI)P60484
BioGRIDPTEN
InParanoidP60484
Interologous Interaction database P60484
IntegromeDBPTEN
STRING (EMBL)PTEN
Ontologies - Pathways
Ontology : AmiGOregulation of cyclin-dependent protein serine/threonine kinase activity  magnesium ion binding  angiogenesis  negative regulation of protein phosphorylation  regulation of B cell apoptotic process  phosphatidylinositol-3-phosphatase activity  phosphoprotein phosphatase activity  protein serine/threonine phosphatase activity  protein tyrosine phosphatase activity  platelet-derived growth factor receptor binding  protein binding  nucleus  nucleolus  cytoplasm  cytoplasm  mitochondrion  cytosol  plasma membrane  protein dephosphorylation  protein dephosphorylation  phospholipid metabolic process  phosphatidylinositol biosynthetic process  apoptotic process  activation of mitotic anaphase-promoting complex activity  epidermal growth factor receptor signaling pathway  neuron-neuron synaptic transmission  synapse assembly  central nervous system development  heart development  aging  response to nutrient  learning or memory  memory  locomotory behavior  protein tyrosine/serine/threonine phosphatase activity  cell proliferation  positive regulation of cell proliferation  negative regulation of cell proliferation  negative regulation of cell proliferation  lipid binding  fibroblast growth factor receptor signaling pathway  response to glucose  cytoplasmic side of plasma membrane  response to zinc ion  regulation of neuron projection development  anaphase-promoting complex binding  negative regulation of phosphatidylinositol 3-kinase signaling  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity  cell migration  PML body  enzyme binding  protein kinase binding  dentate gyrus development  central nervous system neuron axonogenesis  PDZ domain binding  negative regulation of cell migration  negative regulation of myelination  regulation of protein stability  negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle  central nervous system myelin maintenance  response to estradiol  regulation of cellular component size  regulation of myeloid cell apoptotic process  response to ATP  multicellular organismal response to stress  social behavior  peptidyl-tyrosine dephosphorylation  peptidyl-tyrosine dephosphorylation  myelin sheath adaxonal region  Fc-epsilon receptor signaling pathway  response to drug  maternal behavior  cell projection  neuron projection  positive regulation of apoptotic process  negative regulation of apoptotic process  dendritic spine  Schmidt-Lanterman incisure  protein kinase B signaling  endothelial cell migration  inositol phosphate metabolic process  small molecule metabolic process  innate immune response  postsynaptic membrane  response to ethanol  locomotor rhythm  negative regulation of cell size  negative regulation of organ growth  response to arsenic-containing substance  inositol phosphate dephosphorylation  phosphatidylinositol dephosphorylation  phosphatidylinositol dephosphorylation  platelet-derived growth factor receptor signaling pathway  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  cardiac muscle tissue development  forebrain morphogenesis  brain morphogenesis  negative regulation of epithelial cell proliferation  negative regulation of phagocytosis  negative regulation of axonogenesis  protein stabilization  T cell receptor signaling pathway  positive regulation of sequence-specific DNA binding transcription factor activity  inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity  inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity  phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity  phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity  negative regulation of focal adhesion assembly  negative regulation of protein kinase B signaling  rhythmic synaptic transmission  canonical Wnt signaling pathway  synapse maturation  prepulse inhibition  male mating behavior  long-term synaptic potentiation  long term synaptic depression  prostate gland growth  dendritic spine morphogenesis  negative regulation of dendritic spine morphogenesis  negative regulation of ribosome biogenesis  negative regulation of cell aging  negative regulation of excitatory postsynaptic membrane potential  presynaptic membrane assembly  postsynaptic density assembly  positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process  negative regulation of G1/S transition of mitotic cell cycle  positive regulation of excitatory postsynaptic membrane potential  negative regulation of synaptic vesicle clustering  positive regulation of apoptotic signaling pathway  
Ontology : EGO-EBIregulation of cyclin-dependent protein serine/threonine kinase activity  magnesium ion binding  angiogenesis  negative regulation of protein phosphorylation  regulation of B cell apoptotic process  phosphatidylinositol-3-phosphatase activity  phosphoprotein phosphatase activity  protein serine/threonine phosphatase activity  protein tyrosine phosphatase activity  platelet-derived growth factor receptor binding  protein binding  nucleus  nucleolus  cytoplasm  cytoplasm  mitochondrion  cytosol  plasma membrane  protein dephosphorylation  protein dephosphorylation  phospholipid metabolic process  phosphatidylinositol biosynthetic process  apoptotic process  activation of mitotic anaphase-promoting complex activity  epidermal growth factor receptor signaling pathway  neuron-neuron synaptic transmission  synapse assembly  central nervous system development  heart development  aging  response to nutrient  learning or memory  memory  locomotory behavior  protein tyrosine/serine/threonine phosphatase activity  cell proliferation  positive regulation of cell proliferation  negative regulation of cell proliferation  negative regulation of cell proliferation  lipid binding  fibroblast growth factor receptor signaling pathway  response to glucose  cytoplasmic side of plasma membrane  response to zinc ion  regulation of neuron projection development  anaphase-promoting complex binding  negative regulation of phosphatidylinositol 3-kinase signaling  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity  cell migration  PML body  enzyme binding  protein kinase binding  dentate gyrus development  central nervous system neuron axonogenesis  PDZ domain binding  negative regulation of cell migration  negative regulation of myelination  regulation of protein stability  negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle  central nervous system myelin maintenance  response to estradiol  regulation of cellular component size  regulation of myeloid cell apoptotic process  response to ATP  multicellular organismal response to stress  social behavior  peptidyl-tyrosine dephosphorylation  peptidyl-tyrosine dephosphorylation  myelin sheath adaxonal region  Fc-epsilon receptor signaling pathway  response to drug  maternal behavior  cell projection  neuron projection  positive regulation of apoptotic process  negative regulation of apoptotic process  dendritic spine  Schmidt-Lanterman incisure  protein kinase B signaling  endothelial cell migration  inositol phosphate metabolic process  small molecule metabolic process  innate immune response  postsynaptic membrane  response to ethanol  locomotor rhythm  negative regulation of cell size  negative regulation of organ growth  response to arsenic-containing substance  inositol phosphate dephosphorylation  phosphatidylinositol dephosphorylation  phosphatidylinositol dephosphorylation  platelet-derived growth factor receptor signaling pathway  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  cardiac muscle tissue development  forebrain morphogenesis  brain morphogenesis  negative regulation of epithelial cell proliferation  negative regulation of phagocytosis  negative regulation of axonogenesis  protein stabilization  T cell receptor signaling pathway  positive regulation of sequence-specific DNA binding transcription factor activity  inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity  inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity  phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity  phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity  negative regulation of focal adhesion assembly  negative regulation of protein kinase B signaling  rhythmic synaptic transmission  canonical Wnt signaling pathway  synapse maturation  prepulse inhibition  male mating behavior  long-term synaptic potentiation  long term synaptic depression  prostate gland growth  dendritic spine morphogenesis  negative regulation of dendritic spine morphogenesis  negative regulation of ribosome biogenesis  negative regulation of cell aging  negative regulation of excitatory postsynaptic membrane potential  presynaptic membrane assembly  postsynaptic density assembly  positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process  negative regulation of G1/S transition of mitotic cell cycle  positive regulation of excitatory postsynaptic membrane potential  negative regulation of synaptic vesicle clustering  positive regulation of apoptotic signaling pathway  
Pathways : BIOCARTARegulation of eIF4e and p70 S6 Kinase [Genes]    PTEN dependent cell cycle arrest and apoptosis [Genes]    Skeletal muscle hypertrophy is regulated via AKT/mTOR pathway [Genes]    Signaling of Hepatocyte Growth Factor Receptor [Genes]    CTCF: First Multivalent Nuclear Factor [Genes]    mTOR Signaling Pathway [Genes]   
Pathways : KEGGInositol phosphate metabolism    FoxO signaling pathway    Phosphatidylinositol signaling system    p53 signaling pathway    mTOR signaling pathway    PI3K-Akt signaling pathway    Focal adhesion    Tight junction    Hepatitis B    Pathways in cancer    MicroRNAs in cancer    Endometrial cancer    Glioma    Prostate cancer    Melanoma    Small cell lung cancer   
Protein Interaction DatabasePTEN
Wikipedia pathwaysPTEN
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)PTEN
snp3D : Map Gene to Disease5728
SNP (GeneSNP Utah)PTEN
SNP : HGBasePTEN
Genetic variants : HAPMAPPTEN
Exome VariantPTEN
1000_GenomesPTEN 
Cancer Gene: CensusPTEN 
Somatic Mutations in Cancer : COSMICPTEN 
CONAN: Copy Number AnalysisPTEN 
Mutations and Diseases : HGMDPTEN
Genomic VariantsPTEN  PTEN [DGVbeta]
dbVarPTEN
ClinVarPTEN
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM153480    155600    158350    176807    188470    275355    276950    601728    605309    607174    608089    613028   
MedgenPTEN
GENETestsPTEN
Disease Genetic AssociationPTEN
Huge Navigator PTEN [HugePedia]  PTEN [HugeCancerGEM]
General knowledge
Homologs : HomoloGenePTEN
Homology/Alignments : Family Browser (UCSC)PTEN
Phylogenetic Trees/Animal Genes : TreeFamPTEN
Chemical/Protein Interactions : CTD5728
Chemical/Pharm GKB GenePA33942
Drug Sensitivity PTEN
Clinical trialPTEN
Other databases
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=PTEN
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMinePTEN
iHOPPTEN
OncoSearchPTEN

Bibliography

PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.
Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R
Science (New York, N.Y.). 1997 ; 275 (5308) : 1943-1947.
PMID 9072974
 
PTEN: sometimes taking it off can be better than putting it on.
Myers MP, Tonks NK
American journal of human genetics. 1997 ; 61 (6) : 1234-1238.
PMID 9399917
 
Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers.
Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, Tavtigian SV
Nature genetics. 1997 ; 15 (4) : 356-362.
PMID 9090379
 
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.
Marsh DJ, Coulon V, Lunetta KL, Rocca-Serra P, Dahia PL, Zheng Z, Liaw D, Caron S, Duboułę B, Lin AY, Richardson AL, Bonnetblanc JM, Bressieux JM, Cabarrot-Moreau A, Chompret A, Demange L, Eeles RA, Yahanda AM, Fearon ER, Fricker JP, Gorlin RJ, Hodgson SV, Huson S, Lacombe D, Eng C
Human molecular genetics. 1998 ; 7 (3) : 507-515.
PMID 9467011
 
The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate.
Maehama T, Dixon JE
The Journal of biological chemistry. 1998 ; 273 (22) : 13375-13378.
PMID 9593664
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written07-1999Michel Longy

Citation

This paper should be referenced as such :
Longy, M
PTEN (phosphatase and tensin homolog deleted on chromosome ten)
Atlas Genet Cytogenet Oncol Haematol. 1999;3(3):128-129.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/PTENID158.html

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indexed on : Fri Aug 8 11:34:05 CEST 2014

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