PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten)

Identity

Other names	MMAC1 (Mutated in Multiple Advanced Cancer 1)
	TEP 1 (TGFb regulated and Epithelial cell enriched Phosphatase 1)
HGNC	PTEN
Location	10q23.3
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	PTEN   9588
Entrez_Gene	PTEN  5728  phosphatase and tensin homolog
	Cards
Atlas	PTENID158
GeneCards	PTEN
Ensembl	PTEN [Search_View]   ENSG00000171862 [Gene_View]
Genatlas	PTEN
GeneLynx	PTEN
eGenome	PTEN
euGene	5728
	Genomic and cartography
GoldenPath	PTEN  -  10q23.3   chr10:89613175-89718512 +  10q23   [Description]    (hg18-Mar_2006)
Ensembl	PTEN - 10q23 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	PTEN
	Gene and transcription
Genbank	AA017584 [ ENTREZ ]
Genbank	AI825848 [ ENTREZ ]
Genbank	AK021487 [ ENTREZ ]
Genbank	AK021619 [ ENTREZ ]
Genbank	AK024986 [ ENTREZ ]
RefSeq	NM_000314 [ SRS ]    NM_000314 [ ENTREZ ]
RefSeq	AC_000053 [ SRS ]    AC_000053 [ ENTREZ ]
RefSeq	AC_000142 [ SRS ]    AC_000142 [ ENTREZ ]
RefSeq	NC_000010 [ SRS ]    NC_000010 [ ENTREZ ]
RefSeq	NG_007466 [ SRS ]    NG_007466 [ ENTREZ ]
RefSeq	NT_030059 [ SRS ]    NT_030059 [ ENTREZ ]
RefSeq	NW_001838005 [ SRS ]    NW_001838005 [ ENTREZ ]
RefSeq	NW_924884 [ SRS ]    NW_924884 [ ENTREZ ]
AceView	PTEN AceView - NCBI
Unigene	Hs.500466 [ SRS ]    Hs.500466 [ NCBI ]     HS500466 [ spliceNest ]
Fast-db	15227 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P60484 [ SRS]    P60484 [ EXPASY ]     P60484 [ INTERPRO ]     P60484 [ UNIPROT ]
Prosite	PS51182 C2_TENSIN [ SRS ]    PS51182 C2_TENSIN [ Expasy ]
Prosite	PS51181 PPASE_TENSIN [ SRS ]    PS51181 PPASE_TENSIN [ Expasy ]
Interpro	IPR017361 Bifunc_PIno_P3_Pase/Pase_PTEN [ SRS ]    IPR017361 Bifunc_PIno_P3_Pase/Pase_PTEN [ EBI ]
Interpro	IPR014019 Phosphatase_tensin [ SRS ]    IPR014019 Phosphatase_tensin [ EBI ]
Interpro	IPR014020 Tensin_C2 [ SRS ]    IPR014020 Tensin_C2 [ EBI ]
Interpro	IPR000387 Tyr_Pase [ SRS ]    IPR000387 Tyr_Pase [ EBI ]
Interpro	IPR000340 Tyr_Pase_dual_specific [ SRS ]    IPR000340 Tyr_Pase_dual_specific [ EBI ]
Interpro	IPR000242 Tyr_Pase_rcpt/non-rcpt [ SRS ]    IPR000242 Tyr_Pase_rcpt/non-rcpt [ EBI ]
CluSTr	P60484
Pfam	PF00782 DSPc [ SRS ]    PF00782 DSPc [ Sanger ]    pfam00782 [ NCBI-CDD ]
Blocks	P60484
PDB	1D5R [ SRS ]    1D5R [ PdbSum ],   1D5R [ IMB ]   1D5R [ RSDB ]
HPRD	03431
	Protein Interaction databases
DIP	P60484
IntAct	P60484
	Polymorphism : SNP, mutations, diseases
OMIM	137800;153480;158350;174900;176807;176920;188470;276950;601728;605309;607174    [ map ]
GENECLINICS	137800;153480;158350;174900;176807;176920;188470;276950;601728;605309;607174
SNP	PTEN [dbSNP-NCBI]
SNP	NM_000314 [SNP-NCI]
SNP	PTEN [GeneSNPs - Utah]  PTEN] [HGBASE - SRS]
HAPMAP	PTEN [HAPMAP]
COSMIC	PTEN [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	PTEN
	General knowledge
Family Browser	PTEN [UCSC Family Browser]
SOURCE	NM_000314
SMD	Hs.500466
SAGE	Hs.500466
Enzyme	3.1.3.67 [ Enzyme-Expasy ]   3.1.3.67 [ Enzyme-SRS ]   3.1.3.67 [ IntEnz-EBI ]   3.1.3.67 [ BRENDA ]   3.1.3.67 [ KEGG ]   3.1.3.67 [ WIT ]
GO	regulation of cyclin-dependent protein kinase activity [Amigo]  regulation of cyclin-dependent protein kinase activity
GO	angiogenesis [Amigo]  angiogenesis
GO	phosphatidylinositol-3-phosphatase activity [Amigo]  phosphatidylinositol-3-phosphatase activity
GO	protein serine/threonine phosphatase activity [Amigo]  protein serine/threonine phosphatase activity
GO	protein tyrosine phosphatase activity [Amigo]  protein tyrosine phosphatase activity
GO	platelet-derived growth factor receptor binding [Amigo]  platelet-derived growth factor receptor binding
GO	protein binding [Amigo]  protein binding
GO	cytoplasm [Amigo]  cytoplasm
GO	cytoplasm [Amigo]  cytoplasm
GO	cytosol [Amigo]  cytosol
GO	protein amino acid dephosphorylation [Amigo]  protein amino acid dephosphorylation
GO	protein amino acid dephosphorylation [Amigo]  protein amino acid dephosphorylation
GO	lipid metabolic process [Amigo]  lipid metabolic process
GO	induction of apoptosis [Amigo]  induction of apoptosis
GO	central nervous system development [Amigo]  central nervous system development
GO	protein tyrosine/serine/threonine phosphatase activity [Amigo]  protein tyrosine/serine/threonine phosphatase activity
GO	negative regulation of cell proliferation [Amigo]  negative regulation of cell proliferation
GO	lipid binding [Amigo]  lipid binding
GO	phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity [Amigo]  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
GO	phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity [Amigo]  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
GO	hydrolase activity [Amigo]  hydrolase activity
GO	PDZ domain binding [Amigo]  PDZ domain binding
GO	negative regulation of cell migration [Amigo]  negative regulation of cell migration
GO	neurite development [Amigo]  neurite development
GO	regulation of protein stability [Amigo]  regulation of protein stability
GO	negative regulation of apoptosis [Amigo]  negative regulation of apoptosis
GO	endothelial cell migration [Amigo]  endothelial cell migration
GO	negative regulation of cell cycle [Amigo]  negative regulation of cell cycle
GO	inositol phosphate dephosphorylation [Amigo]  inositol phosphate dephosphorylation
GO	phosphoinositide dephosphorylation [Amigo]  phosphoinositide dephosphorylation
GO	platelet-derived growth factor receptor signaling pathway [Amigo]  platelet-derived growth factor receptor signaling pathway
GO	cardiac muscle development [Amigo]  cardiac muscle development
GO	inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity [Amigo]  inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
GO	phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity [Amigo]  phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
GO	negative regulation of focal adhesion formation [Amigo]  negative regulation of focal adhesion formation
GO	negative regulation of protein kinase B signaling cascade [Amigo]  negative regulation of protein kinase B signaling cascade
BIOCARTA	CTCF: First Multivalent Nuclear Factor    [Genes]
BIOCARTA	Regulation of eIF4e and p70 S6 Kinase    [Genes]
BIOCARTA	Skeletal muscle hypertrophy is regulated via AKT/mTOR pathway    [Genes]
BIOCARTA	mTOR Signaling Pathway    [Genes]
BIOCARTA	Signaling of Hepatocyte Growth Factor Receptor    [Genes]
BIOCARTA	PTEN dependent cell cycle arrest and apoptosis    [Genes]
KEGG	Inositol phosphate metabolism
KEGG	Phosphatidylinositol signaling system
KEGG	Focal adhesion
KEGG	Tight junction
PubGene	PTEN
TreeFam	PTEN
CTD	5728 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	PTEN Related clones (RZPD - Berlin)
	PubMed
PubMed	439 Pubmed reference(s) in LocusLink

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 articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	07-1999	Michel 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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:16:45 2008