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FLASH GENE
Symbol PTEN contributors: mct - updated : 14-01-2010
HGNC name phosphatase and tensin homolog (mutated in multiple advanced cancers 1)
HGNC id 9588
Corresponding disease
BZS Bannayan-Zonana syndrome
JPS2 juvenile polyposis syndrome
MCAUTS macrocephaly extreme (>4DS) / autism
MHAM Cowden syndrome
PROTLS Proteus-like syndrome
Location 10q23.31      Physical location : 89.623.194 - 89.728.531
Synonym name
  • mutated in multiple advanced cancers 1
  • MMAC1 phosphatase and tensin homolog deleted on chromosome 10
    • Synonym symbol(s) MMAC1, PTH1, TEP1, BZS, PTEN1, MGC11227
    EC.number 3.1.3.48, 3.1.3.16, 3.1.3.67
    DNA
    TYPE functioning gene
    STRUCTURE 105.34 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    KIAA0261 10q23.31 KIAA0261 LOC340749 10q23.31 similar to Rpl7a protein OPN4 10q22 opsin 4 (melanopsin) LDB3 10q22.3-q23.2 LIM domain binding 3 BMPR1A 10q22.3-q23.2 bone morphogenetic protein receptor, type IA EMILIN3 10q23.31 elastin microfibril interfacer 3 SNCG 10q26.2-q23.3 synuclein, gamma (breast cancer-specific protein 1) APM2 10q23.31 adipose specific 2 KIAA1975 10q23.31 KIAA1975 protein similar to MRIP2 GLUD1 10q23.3 glutamate dehydrogenase 1 MGC5560 10q23.31 hypothetical protein MGC5560 LOC389991 10 similar to synaptotagmin XV isoform a; chr10 synaptotagmin FAM22A 10q23.31 family with sequence similarity 22, member A LOC387697 10 LOC387697 LOC387698 10 similar to KIAA2020 protein LOC118945 10q23.31 similar to Cathepsin L preproprotein MINPP1 10q23.3 multiple inositol polyphosphate histidine phosphatase, 1 PAPSS2 10q23-q23.2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 FLJ14600 10q23.31 hypothetical protein FLJ14600 MGC35136 10q23.31 hypothetical protein MGC35136 PTEN 10q23.3 phosphatase and tensin homolog (mutated in multiple advanced cancers 1) FLJ11218 10q23.31 hypothetical protein FLJ11218 LOC142910 10q23.31 similar to Triacylglycerol lipase, gastric precursor (Gastric lipase) (GL) LOC389992 10 similar to ribosomal protein L7 LIPF 10q23.33 lipase, gastric LOC118934 10q23.31 similar to hypothetical protein 9930115F20 LOC389993 10 similar to lipase A precursor; Lipase A, lysosomal acid, cholesterol esterase LOC340654 10q23.31 similar to bA304I5.1 (novel lipase) MGC22805 10q23.31-q23.32 hypothetical protein MGC22805 AMSH-LP 10q23.33 associated molecule with the SH3 domain of STAM (AMSH) like protein DKFZp761K1824 10q23.32 hypothetical protein DKFZp761K1824 ACTA2 10q22.3-q23.1 actin, alpha 2, smooth muscle, aorta TNFRSF6 10q24.1 tumor necrosis factor receptor superfamily, member 6 CH25H 10q23 cholesterol 25-hydroxylase LIPA 10q23.2-q23.3 lipase A, lysosomal acid, cholesterol esterase (Wolman disease) IFIT2 10q23.3 interferon-induced protein with tetratricopeptide repeats 2 IFIT4 10q23.3 interferon-induced protein with tetratricopeptide repeats 4 LOC389994 10 similar to Interferon-induced protein with tetratricopeptide repeats 1 (IFIT-1) (Interferon-induced 56 kDa protein) (IFI-56K)
    RNA
    TRANSCRIPTS type messenger
    text alternatively spliced (PMID: 10978354)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 5572 - 403 - -
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepharynx   highly
    Endocrineparathyroid   highly
    Hearing/Equilibriumearinnercochlea highly
    Lymphoid/Immunelymph node   highly
    Nervousbrainlimbic systemhippocampus highly Homo sapiens
     brain   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connective   highly
    Connectiveadipose  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines glioblastoma cell line
    fluid/secretion
    at STAGE
    physiological period embryo
    Text development tissue (skin, thyroid, central nervous system, peripheral nervous system, autonomomic nervous system and gastroiintestinal tract)
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a large region of homology with chicken tensin and auxilin
  • a C-terminal region with PEST sequence and a PDZ binding motif, a typical PDZ domain-binding motif that interacts with several PDZ domain-containing proteins
    • mono polymer monomer
    HOMOLOGY
    interspecies homolog to C.elegans C25A1.3
    homolog to rattus Pten (99.50 pc)
    homolog to murine Pten (99.75 pc)
    intraspecies homolog to phosphatase
    homolog to tensin
    Homologene
    FAMILY
  • non-receptor class of protein-tissue phosphate family
    • CATEGORY enzyme , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • localizes to the nucleus coincident with the G0-G1 phases of the cell cycle and compartmentalization may regulate cell cycle progression dependent upon the down-regulation of cyclin D1
  • nuclear PTEN down-regulates cyclin D1 transcription and this event is mediated by the down-regulation of MAPK specifically by nuclear localized PTEN
    • basic FUNCTION
  • lipid phosphatase, antagonizing signal transduction downstream of PI-3 kinase by dephosphorylating phosphatidylinositol-triphosphate (PtdInsP) and suppression of cell growth through the negative regulation of cell cycle and cell survival
  • modulating cell cycle progression and cell survival (blockage) through down-regulating the positive cell cycle-regulator (cycle D1) by its phosphatase activity and up-regulating the negative cell cycle regulator p21 (by its lipid phosphatase activity)
  • negative regulator of cell interactions with the extracellular matrix
  • negative regulator of PI3 kinase signaling, alters tau phosphorylation in cells by mechanisms independent of GSK-3
  • control of tumor-induced angiogenesis
  • nuclear PTEN plays a role through cell cycle suppression functions in regulating carcinogenesis
  • playing a fundamental role in the maintenance of chromosomal stability through the physical interaction with centromeres and control of DNA repair
  • a potential role of acetylation in regulating PTEN function
  • may safeguard against developing malignant tumors in patients with TSC deficiency
  • regulated signalling molecule at the synapse, which is recruited to the postsynaptic membrane upon NMDA receptor activation, and is required for the modulation of synaptic activity during plasticity
  • regulated component of the intracellular signalling machinery that controls synaptic transmission and plasticity at hippocampal excitatory synapses
  • may be having a specific postsynaptic function at excitatory hippocampal synapses, and potential critical mediator of long-term depression in hippocampal neurons
  • nuclear phophatase of a transcription factor
    • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, genomic integrity
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism lipid/lipoprotein
    signaling signal transduction
  • PI3K pathway
  • molecular pathway PTEN-CEBPA-CTNNA1 which is evolutionarily conserved, and controls myeloid development and transformation
    • a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor,
  • Mg2+
    • protein
  • MAPK, blocks MAPK, phosphorylation by inhibiting the phosphorylation of IRS1 (down regulation of cyclin D1)
  • PI3K/AKT implicating cell death and/or cell cycle arrest
  • stimulating TNFSF10 through FOXO3 activation
  • interacting with STK11
  • negative regulator of the PI3K pathway, that is a key downstream target of NEDD4 (NEDD4-regulated PTEN is a key regulator of terminal arborization)
  • interacting with EGR1 (EGR1–PTEN network was found to influence synovial sarcoma cell survival, showing that SS18–SSX-mediated attenuation of this pathway enables these cells to escape cell death)
  • association between PTEN and DLG4, association that requires the PDZ motif at the PTEN C-terminus
  • CREB1 is a protein target of PTEN phosphatase and PTEN deficiency leads to CREB1 phosphorylation independent of the PI3K/AKT pathway (MID: 21385900)
  • PTEN and PIKFYVE are two major players in phagosomal PtdIns(3)P metabolism
    • cell & other
    REGULATION
    activated by lovastatin that may signal through PPARgamma and directly upregulate PTEN expression at the transcriptional level
    SREBF1, known to induce PPAR gamma expression
    induced by BMP2 (through stimulation of the SMAD pathway)
    inhibited by phosphorylation
    oxidation of the cysteine at the phosphatase active site
    Other downregulation playing a role in inactivation in thyroid cancer
    phosphorylated by STK11
    stability negatively regulated by polyubiquitination catalyzed by NEDD4-1
    up-regulated by HIF1alpha in absence of TSC2
    ASSOCIATED DISORDERS
    corresponding disease(s) BZS , JPS2 , MHAM , PROTLS , MCAUTS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   insertion    
    insertion/deletion in endometrial carcinomas, deletion in thyroid cancers (or transient ectopic expression)
    constitutional germinal mutation      
    in PTEN-hamartoma syndrome (Proteus-Proteus-like syndrome, Bannayan and Cowden syndrome), and in VATER association with hydrocephaly
    tumoral   LOH    
    in hepatocellular carcinoma
    tumoral       loss of function
    in hamartoma, glioma, uterus carcinoma
    tumoral       loss of function
    in Bannayan and Cowden syndrome
    tumoral germinal mutation      
    in Lhermitte-Duclos disease (LDD) , a rare cerebellar tumor associated with Cowden disease
    tumoral       loss of function
    in deficient intestinal stem cells and initiate intestinal polyposis
    tumoral     --low  
    in melanomas
    constitutional germinal mutation      
    heterozygous Arg234Gln in a patient with brain tumors of multiple lineages
    tumoral   deletion    
    Loss of PTEN and concomitant activation of AKTcould act in partnership with the TMPRSS2-ERG fusion protein to promote progression to prostatecancer
    Susceptibility to Autism spectrum disorder
    Variant & Polymorphism other haploinsufficiency for PTEN may be a genetic risk factor for abnormal brain development in response to exposure to environmental toxins that impinge on the PI3K pathway
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS