Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Pten. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. [provided by RefSeq, Jul 2008]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Pten
  • participates in the following biological processes:
    • dephosphorylation ^[21]
  • performs the following molecular functions:
    • phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity ^[21]
  • is located in the following cellular components:
    • cytoplasm ^{[3, 25]}
    • myelin sheath adaxonal region ^[15]
    • neuron projection ^[24]
    • nucleus ^{[1, 3, 25]}
    • Schmidt-Lanterman incisure ^[15]
• The gene product of Pten has been shown to bind to the gene products of Cenpc1, Slc9a3r1, Slc9a3r2, Ypel1. ^{[2, 17, 19, 23]} Researchers have inferred, based on physical interactions, that the gene product of Pten
  • performs the following molecular functions:
    • protein kinase binding ^[26]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Pten
  • participates in the following biological processes:
    • activation of mitotic anaphase-promoting complex activity ^[20]
    • angiogenesis ^[6]
    • brain morphogenesis ^[16]
    • cardiac muscle tissue development ^[6]
    • cell migration ^[13]
    • central nervous system development ^[13]
    • central nervous system myelin maintenance ^[4]
    • central nervous system neuron axonogenesis ^[8]
    • dendritic spine morphogenesis ^{[4, 9]}
    • dentate gyrus development ^[14]
    • endothelial cell migration ^[6]
    • forebrain morphogenesis ^[8]
    • heart development ^[5]
    • induction of apoptosis ^[21]
    • learning or memory ^[8]
    • locomotor rhythm ^[14]
    • locomotory behavior ^[8]
    • long-term synaptic potentiation ^[4]
    • male mating behavior ^[8]
    • maternal behavior ^[8]
    • multicellular organismal response to stress ^[8]
    • negative regulation of apoptotic process ^[22]
    • negative regulation of axonogenesis ^[8]
    • negative regulation of cell aging ^[20]
    • negative regulation of cell proliferation ^[12]
    • negative regulation of cell size ^{[8, 9]}
    • negative regulation of dendritic spine morphogenesis ^[8]
    • negative regulation of epithelial cell proliferation ^[11]
    • negative regulation of excitatory postsynaptic membrane potential ^[9]
    • negative regulation of myelination ^[2]
    • negative regulation of organ growth ^[16]
    • negative regulation of protein kinase B signaling cascade ^{[2, 8, 22]}
    • negative regulation of ribosome biogenesis ^[4]
    • negative regulation of synaptic vesicle clustering ^{[4, 8]}
    • neuron-neuron synaptic transmission ^[4]
    • positive regulation of cell proliferation ^[20]
    • positive regulation of excitatory postsynaptic membrane potential ^[4]
    • postsynaptic density assembly ^[4]
    • prepulse inhibition ^{[8, 16]}
    • presynaptic membrane assembly ^[4]
    • prostate gland growth ^[11]
    • protein kinase B signaling cascade ^[26]
    • regulation of B cell apoptotic process ^[18]
    • regulation of cellular component size ^[4]
    • regulation of myeloid cell apoptotic process ^[18]
    • regulation of neuron projection development ^[7]
    • rhythmic synaptic transmission ^[14]
    • social behavior ^{[8, 16]}
    • synapse assembly ^[8]
    • synapse maturation ^[4]
  • is located in the following cellular components:
    • intracellular ^[26]
• Researchers have inferred, based on genetic interactions, that the gene product of Pten
  • participates in the following biological processes:
    • negative regulation of cell proliferation based on interactions with Tsc2 ^[10]
    • regulation of cell cycle based on interactions with Trp53 ^[1]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Pten:
  • participates in the following biological processes:
    • activation of mitotic anaphase-promoting complex activity
    • canonical Wnt receptor signaling pathway
    • inositol phosphate dephosphorylation
    • long term synaptic depression
    • memory
    • negative regulation of cell migration
    • negative regulation of cell proliferation
    • negative regulation of cyclin-dependent protein kinase activity involved in G1/S
    • negative regulation of focal adhesion assembly
    • negative regulation of G1/S transition of mitotic cell cycle
    • negative regulation of phagocytosis
    • negative regulation of protein kinase B signaling cascade
    • negative regulation of protein phosphorylation
    • neuron projection development
    • peptidyl-tyrosine dephosphorylation
    • phosphatidylinositol dephosphorylation
    • platelet-derived growth factor receptor signaling pathway
    • positive regulation of apoptotic process
    • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
    • positive regulation of sequence-specific DNA binding transcription factor activity
    • protein dephosphorylation
    • protein stabilization
    • regulation of protein stability
  • performs the following molecular functions:
    • anaphase-promoting complex binding
    • enzyme binding
    • inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
    • PDZ domain binding
    • phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
    • phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
    • phosphatidylinositol-3-phosphatase activity
    • phosphoprotein phosphatase activity
    • platelet-derived growth factor receptor binding
    • protein serine/threonine phosphatase activity
    • protein tyrosine phosphatase activity
  • is located in the following cellular components:
    • cell projection
    • cytoplasm
    • dendritic spine
    • internal side of plasma membrane
    • mitochondrion
    • neuron projection
    • nucleus
    • plasma membrane
    • postsynaptic membrane

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Summary text based on GO annotations supported by structural data

• Pten encodes a protein or proteins that contain the following InterPro domains: Bifunctional phosphatidylinositol trisphosphate phosphatase/dual-specificity phosphatase PTEN, C2 calcium/lipid-binding domain, CaLB, Dual specificity phosphatase, catalytic domain, Phosphatase tensin type, Protein-tyrosine phosphatase, active site, Tensin phosphatase, C2 domain, indicating that the gene product:
  • performs the following molecular functions:
    • magnesium ion binding
    • phosphatase activity
    • protein tyrosine/serine/threonine phosphatase activity

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Pten indicates that it:
  • participates in the following biological processes:
    • apoptotic process
    • lipid metabolic process
    • nervous system development
  • performs the following molecular functions:
    • hydrolase activity

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References

1. Chang CJ et al. (2008) PTEN nuclear localization is regulated by oxidative stress and mediates p53-dependent tumor suppression. Mol Cell Biol, 28:3281-9. (PubMed:18332125)
2. Cotter L et al. (2010) Dlg1-PTEN interaction regulates myelin thickness to prevent damaging peripheral nerve overmyelination. Science, 328:1415-8. (PubMed:20448149)
3. Fouladkou F et al. (2008) The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization. Proc Natl Acad Sci U S A, 105:8585-90. (PubMed:18562292)
4. Fraser MM et al. (2008) Phosphatase and tensin homolog, deleted on chromosome 10 deficiency in brain causes defects in synaptic structure, transmission and plasticity, and myelination abnormalities. Neuroscience, 151:476-488. (PubMed:18082964)
5. Garcia-Garcia MJ et al. (2005) Inaugural Article: Analysis of mouse embryonic patterning and morphogenesis by forward genetics. Proc Natl Acad Sci U S A, 102:5913-9. (PubMed:15755804)
6. Hamada K et al. (2005) The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis. Genes Dev, 19:2054-65. (PubMed:16107612)
7. Kim JY et al. (2009) DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212. Neuron, 63:761-73. (PubMed:19778506)
8. Kwon CH et al. (2006) Pten regulates neuronal arborization and social interaction in mice. Neuron, 50:377-88. (PubMed:16675393)
9. Luikart BW et al. (2011) Pten knockdown in vivo increases excitatory drive onto dentate granule cells. J Neurosci, 31:4345-54. (PubMed:21411674)
10. Ma L et al. (2005) Genetic analysis of Pten and Tsc2 functional interactions in the mouse reveals asymmetrical haploinsufficiency in tumor suppression. Genes Dev, 19:1779-86. (PubMed:16027168)
11. Ma X et al. (2005) Targeted biallelic inactivation of Pten in the mouse prostate leads to prostate cancer accompanied by increased epithelial cell proliferation but not by reduced apoptosis. Cancer Res, 65:5730-9. (PubMed:15994948)
12. Manning BD et al. (2005) Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2. Genes Dev, 19:1773-8. (PubMed:16027169)
13. Marino S et al. (2002) PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum. Development, 129:3513-22. (PubMed:12091320)
14. Ogawa S et al. (2007) A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice. Brain Res, 1168:112-23. (PubMed:17706614)
15. Ozcelik M et al. (2010) Pals1 is a major regulator of the epithelial-like polarization and the extension of the myelin sheath in peripheral nerves. J Neurosci, 30:4120-31. (PubMed:20237282)
16. Page DT et al. (2009) Haploinsufficiency for Pten and Serotonin transporter cooperatively influences brain size and social behavior. Proc Natl Acad Sci U S A, 106:1989-94. (PubMed:19208814)
17. Pan Y et al. (2008) Na+/H+ exchanger regulatory factor 1 inhibits platelet-derived growth factor signaling in breast cancer cells. Breast Cancer Res, 10:R5. (PubMed:18190691)
18. Podsypanina K et al. (1999) Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proc Natl Acad Sci U S A, 96:1563-8. (PubMed:9990064)
19. Shen WH et al. (2007) Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell, 128:157-70. (PubMed:17218262)
20. Song MS et al. (2011) Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. Cell, 144:187-99. (PubMed:21241890)
21. Stambolic V et al. (1998) Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell, 95:29-39. (PubMed:9778245)
22. Sun H et al. (1999) PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway. Proc Natl Acad Sci U S A, 96:6199-204. (PubMed:10339565)
23. Takahashi Y et al. (2006) PTEN tumor suppressor associates with NHERF proteins to attenuate PDGF receptor signaling. EMBO J, 25:910-20. (PubMed:16456542)
24. Ventruti A et al. (2011) Reelin deficiency causes specific defects in the molecular composition of the synapses in the adult brain. Neuroscience, 189:32-42. (PubMed:21664258)
25. Wang S et al. (2003) Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell, 4:209-21. (PubMed:14522255)
26. Xu D et al. (2010) Regulation of PTEN stability and activity by Plk3. J Biol Chem, 285:39935-42. (PubMed:20940307)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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