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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
Location 10q23.3
Location_base_pair Starts at 89613175 and ends at 89718512 bp from pter ( according to hg18-Mar_2006)  [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
  

External links

Nomenclature
HGNC (Hugo)PTEN   9588
Entrez_Gene (NCBI)PTEN  5728  phosphatase and tensin homolog
Cards
AtlasPTENID158
GeneCards (Weizmann)PTEN
Ensembl (Hinxton)ENSG00000171862 [Gene_View]  PTEN [Vega]
AceView (NCBI)PTEN
Genatlas (Paris)PTEN
euGene (Indiana)5728
SOURCE (Stanford)NM_000314
Genomic and cartography
GoldenPath (UCSC)PTEN  -  10q23.3   chr10:89613175-89718512 +  10q23   [Description]    (hg18-Mar_2006)
EnsemblPTEN - 10q23 [CytoView]
Mapping of homologs : NCBIPTEN [Mapview]
OMIM137800   153480   158350   174900   176807   176920   188470   276950   601728   605309   607174   612242   
Gene and transcription
Gene : Genbank (Entrez)AA017584 AI825848 AK021487 AK021619 AK024986
Reference sequence (RefSeq transcript) :SRSNM_000314
Reference transcript : EntrezNM_000314
RefSeq genomic : SRSAC_000053 AC_000142 NC_000010 NG_007466 NT_030059 NW_001838005 NW_924884
RefSeq genomic : EntrezAC_000053 AC_000142 NC_000010 NG_007466 NT_030059 NW_001838005 NW_924884
Consensus coding sequences : CCDS NCBIPTEN
Cluster EST : UnigeneHs.500466 [ SRS ] Hs.500466 [ NCBI ]
Alternative Splicing : Fast-db (Paris)15227
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtP60484 (SRS) P60484 (Expasy) P60484 (Uniprot)
With graphics : InterProP60484
Splice isoforms : VarSplice FASTAP60484(VarSplice FASTA)
Domaine pattern : Prosite (SRS)C2_TENSIN (PS51182)    PPASE_TENSIN (PS51181)   
Domain pattern : Prosite (Expaxy)C2_TENSIN (PS51182)    PPASE_TENSIN (PS51181)   
Domains : Interpro (SRS)Bifunc_PIno_P3_Pase/Pase_PTEN    Phosphatase_tensin    Tensin_C2    Tyr_Pase    Tyr_Pase_dual_specific    Tyr_Pase_rcpt/non-rcpt   
Domains : Interpro (EBI)Bifunc_PIno_P3_Pase/Pase_PTEN    Phosphatase_tensin    Tensin_C2    Tyr_Pase    Tyr_Pase_dual_specific    Tyr_Pase_rcpt/non-rcpt   
Related proteins : CluSTrP60484
Domain families : Pfam SRSDSPc (PF00782)   
Domain families : Pfam SangerDSPc (PF00782)   
Domain families : Pfam NCBIpfam00782   
Blocks (Seattle)P60484
Crystal structure of protein : PDB SRS1D5R   
Crystal structure of protein : PDBSum1D5R   
Crystal structure of protein : IMB1D5R   
Crystal structure of protein : PDB RSDB1D5R   
HPRD03431
Protein Interaction databases
DIP (DOE-UCLA)P60484
IntAct (EBI)P60484
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIPTEN
SNP : GeneSNP UtahPTEN
SNP : HGBasePTEN
Genetic variants : HAPMAPPTEN
Somatic Mutations in Cancer : COSMICPTEN 
Mutations and Diseases : HGMDPTEN
Hereditary diseases : OMIM137800    153480    158350    174900    176807    176920    188470    276950    601728    605309    607174    612242   
Hereditary diseases : GENETests137800    153480    158350    174900    176807    176920    188470    276950    601728    605309    607174    612242   
Diseases : Genetic AssociationPTEN
General knowledge
Homologs : HomoloGenePTEN
Homology/Alignments : Family Browser UCSCPTEN
Phylogenetic Trees/Animal Genes : TreeFamPTEN
Catalytic activity : Enzyme3.1.3.67 [ Enzyme-Expasy ]   3.1.3.67 [ Enzyme-SRS ]   3.1.3.67 [ IntEnz-EBI ]   3.1.3.67 [ BRENDA ]   3.1.3.67 [ KEGG ]   
Chemical/Protein Interactions : CTD5728
Keywords Ontology : AmiGOregulation of cyclin-dependent protein kinase activity  magnesium ion binding  angiogenesis  phosphatidylinositol-3-phosphatase activity  protein serine/threonine phosphatase activity  protein tyrosine phosphatase activity  platelet-derived growth factor receptor binding  protein binding  nucleus  cytoplasm  cytoplasm  cytosol  protein amino acid dephosphorylation  protein amino acid dephosphorylation  lipid metabolic process  induction of apoptosis  central nervous system development  protein tyrosine/serine/threonine phosphatase activity  negative regulation of cell proliferation  lipid binding  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity  hydrolase activity  PDZ domain binding  negative regulation of cell migration  neurite development  regulation of protein stability  negative regulation of apoptosis  endothelial cell migration  negative regulation of cell cycle  inositol phosphate dephosphorylation  phosphoinositide dephosphorylation  platelet-derived growth factor receptor signaling pathway  cardiac muscle development  inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity  phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity  negative regulation of focal adhesion formation  negative regulation of protein kinase B signaling cascade  
Keywords Ontology : EGO-EBIregulation of cyclin-dependent protein kinase activity  magnesium ion binding  angiogenesis  phosphatidylinositol-3-phosphatase activity  protein serine/threonine phosphatase activity  protein tyrosine phosphatase activity  platelet-derived growth factor receptor binding  protein binding  nucleus  cytoplasm  cytoplasm  cytosol  protein amino acid dephosphorylation  protein amino acid dephosphorylation  lipid metabolic process  induction of apoptosis  central nervous system development  protein tyrosine/serine/threonine phosphatase activity  negative regulation of cell proliferation  lipid binding  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity  hydrolase activity  PDZ domain binding  negative regulation of cell migration  neurite development  regulation of protein stability  negative regulation of apoptosis  endothelial cell migration  negative regulation of cell cycle  inositol phosphate dephosphorylation  phosphoinositide dephosphorylation  platelet-derived growth factor receptor signaling pathway  cardiac muscle development  inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity  phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity  negative regulation of focal adhesion formation  negative regulation of protein kinase B signaling cascade  
Pathways : BIOCARTACTCF: First Multivalent Nuclear Factor [Genes]    Regulation of eIF4e and p70 S6 Kinase [Genes]    Skeletal muscle hypertrophy is regulated via AKT/mTOR pathway [Genes]    mTOR Signaling Pathway [Genes]    Signaling of Hepatocyte Growth Factor Receptor [Genes]    PTEN dependent cell cycle arrest and apoptosis [Genes]   
Pathways : KEGGInositol phosphate metabolismPhosphatidylinositol signaling systemFocal adhesionTight junction
Other databases
Probes
Probes : ImagenesPTEN Related clones (RZPD - Berlin)
Literature
PubMed499 Pubmed reference(s) in Entrez
PubGenePTEN

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, Dubouˆ© 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. July 1999 .
URL : http://AtlasGeneticsOncology.org/Genes/PTENID158.html

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indexed on : Sat Jun 27 16:42:37 CEST 2009

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