Phosphatase and tensin homolog |
Crystallographic structure of human PTEN. The N-terminal phosphatase domain is colored blue while the C-terminal C2 domain is colored red.[1] |
Available structures |
PDB |
Ortholog search: PDBe, RCSB |
List of PDB id codes |
1D5R, 2KYL, 4O1V
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Identifiers |
Symbols |
PTEN ; 10q23del; BZS; CWS1; DEC; GLM2; MHAM; MMAC1; PTEN1; TEP1 |
External IDs |
OMIM: 601728 HomoloGene: 265 GeneCards: PTEN Gene |
EC number |
3.1.3.16, 3.1.3.48, 3.1.3.67 |
Gene ontology |
Molecular function |
• magnesium ion binding
• phosphatidylinositol-3-phosphatase activity
• phosphoprotein phosphatase activity
• protein serine/threonine phosphatase activity
• protein tyrosine phosphatase activity
• platelet-derived growth factor receptor binding
• protein binding
• protein tyrosine/serine/threonine phosphatase activity
• lipid binding
• anaphase-promoting complex binding
• phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
• enzyme binding
• protein kinase binding
• PDZ domain binding
• inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
• phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
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Cellular component |
• nucleus
• nucleolus
• cytoplasm
• mitochondrion
• cytosol
• plasma membrane
• cytoplasmic side of plasma membrane
• PML body
• myelin sheath adaxonal region
• cell projection
• neuron projection
• dendritic spine
• Schmidt-Lanterman incisure
• postsynaptic membrane
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Biological process |
• regulation of cyclin-dependent protein serine/threonine kinase activity
• angiogenesis
• negative regulation of protein phosphorylation
• regulation of B cell apoptotic process
• 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
• cell proliferation
• positive regulation of cell proliferation
• negative regulation of cell proliferation
• fibroblast growth factor receptor signaling pathway
• response to glucose
• response to zinc ion
• regulation of neuron projection development
• negative regulation of phosphatidylinositol 3-kinase signaling
• cell migration
• dentate gyrus development
• central nervous system neuron axonogenesis
• 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
• Fc-epsilon receptor signaling pathway
• response to drug
• maternal behavior
• positive regulation of apoptotic process
• negative regulation of apoptotic process
• protein kinase B signaling
• endothelial cell migration
• inositol phosphate metabolic process
• small molecule metabolic process
• innate immune response
• 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
• 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
• 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
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Sources: Amigo / QuickGO |
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Orthologs |
Species |
Human |
Mouse |
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Entrez |
5728 |
19211 |
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Ensembl |
ENSG00000171862 |
ENSMUSG00000013663 |
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UniProt |
P60484 |
O08586 |
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RefSeq (mRNA) |
NM_000314 |
NM_008960 |
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RefSeq (protein) |
NP_000305 |
NP_032986 |
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Location (UCSC) |
Chr 10:
89.62 – 89.73 Mb |
Chr 19:
32.76 – 32.83 Mb |
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PubMed search |
[1] |
[2] |
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Space-filling model of the PTEN protein (blue) complexed with tartaric acid (brown).
[1]
Phosphatase and tensin homolog (PTEN) is a protein that, in humans, is encoded by the PTEN gene.[2] Mutations of this gene are a step in the development of many cancers.
PTEN acts as a tumor suppressor gene through the action of its phosphatase protein product. This phosphatase is involved in the regulation of the cell cycle, preventing cells from growing and dividing too rapidly.[3] It is one of the targets for drug candidates such as the oncomiR, MIRN21.
This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by 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.[4]
Contents
- 1 Function and structure
- 2 Clinical significance
- 2.1 Cancers
- 2.2 Non-cancerous neoplasia
- 2.3 Brain function and autism
- 2.4 Cell regeneration
- 3 Cell lines
- 4 Interactions
- 5 See also
- 6 References
- 7 Further reading
- 8 External links
Function and structure
The corresponding PTEN protein is found in almost all tissues in the body. PTEN protein acts as a phosphatase to dephosphorylate phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5)P3 or PIP3). PTEN specifically catalyses the dephosporylation of the 3` phosphate of the inositol ring in PIP3, resulting in the biphosphate product PIP2 (PtdIns(4,5)P2). This dephosphorylation is important because it results in inhibition of the AKT signaling pathway.
The structure of PTEN (solved by X-ray crystallography, see figure to the upper right[1]) reveals that it consists of a phosphatase domain, and a C2 domain: the phosphatase domain contains the active site, which carries out the enzymatic function of the protein, while the C2 domain binds the phospholipid membrane. Thus PTEN binds the membrane through its C2 domain, bringing the active site to the membrane-bound PIP3 to de-phosphorylate it.
When the PTEN enzyme is functioning properly, it acts as part of a chemical pathway that signals cells to stop dividing and can cause cells to undergo programmed cell death (apoptosis) when necessary. These functions prevent uncontrolled cell growth that can lead to the formation of tumors. There is also evidence that the protein made by the PTEN gene may play a role in cell movement (migration) and adhesion of cells to surrounding tissues.
PTEN orthologs[5] have been identified in most mammals for which complete genome data are available.
Clinical significance
Cancers
PTEN is one of the most commonly lost tumor suppressors in human cancer; in fact, up to 70% of men with prostate cancer are estimated to have lost a copy of the PTEN gene at the time of diagnosis.[6]
During tumor development, mutations and deletions of PTEN occur that inactivate its enzymatic activity leading to increased cell proliferation and reduced cell death. Frequent genetic inactivation of PTEN occurs in glioblastoma, endometrial cancer, and prostate cancer; and reduced expression is found in many other tumor types such as lung and breast cancer. Furthermore, PTEN mutation also causes a variety of inherited predispositions to cancer.
Non-cancerous neoplasia
Researchers have identified more than 70 mutations in the PTEN gene in people with Cowden syndrome.[citation needed] These mutations can be changes in a small number of base pairs or, in some cases, deletions of a large number of base pairs.[citation needed] Most of these mutations cause the PTEN gene to make a protein that does not function properly or does not work at all. The defective protein is unable to stop cell division or signal abnormal cells to die, which can lead to tumor growth, particularly in the breast, thyroid, or uterus.[7]
Mutations in the PTEN gene cause several other disorders that, like Cowden syndrome, are characterized by the development of non-cancerous tumors called hamartomas. These disorders include Bannayan-Riley-Ruvalcaba syndrome and Proteus-like syndrome. Together, the disorders caused by PTEN mutations are called PTEN hamartoma tumor syndromes, or PHTS. Mutations responsible for these syndromes cause the resulting protein to be non-functional or absent. The defective protein allows the cell to divide in an uncontrolled way and prevents damaged cells from dying, which can lead to the growth of tumors.[7]
Brain function and autism
Defects of the PTEN gene have been cited to be a potential cause of autism spectrum disorders.[8] When defective, PTEN protein interacts with the protein of a second gene known as Tp53 to dampen energy production in neurons. This severe stress leads to a spike in harmful mitochondrial DNA changes and abnormal levels of energy production in the cerebellum and hippocampus, brain regions critical for social behavior and cognition. When PTEN protein is insufficient, its interaction with p53 triggers deficiencies and defects in other proteins that also have been found in patients with learning disabilities including autism.[8]
Patients with defective PTEN can develop cerebellar mass lesions called dysplastic gangliocytomas or Lhermitte–Duclos disease.[7]
Cell regeneration
PTEN's strong link to cell growth inhibition is being studied as a possible therapeutic target in tissues that do not traditionally regenerate in mature animals, such as central neurons. PTEN deletion mutants have recently[9] been shown to allow nerve regeneration in mice.[10]
Cell lines
Cell lines with known PTEN mutations include:
- prostate: LNCaP, PC-3
- kidney: 786-O
- glioblastoma: U87MG[11]
- breast : MB-MDA-468, BT549[11]
- bladder: J82, UMUC-3
Interactions
PTEN (gene) has been shown to interact with:
- CSNK2A2,[12]
- CSNK2A1,[12]
- MAGI3[13]
- MVP,[14]
- NEDD4,[15]
- NR3C4,[16]
- P53,[17] and
- PTK2.[18][19]
See also
- Multiple hamartoma syndrome
References
- ^ a b c PDB 1d5r; Lee JO, Yang H, Georgescu MM, Di Cristofano A, Maehama T, Shi Y, Dixon JE, Pandolfi P, Pavletich NP (October 1999). "Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association". Cell 99 (3): 323–34. doi:10.1016/S0092-8674(00)81663-3. PMID 10555148.
- ^ 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 (April 1997). "Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers". Nat. Genet. 15 (4): 356–62. doi:10.1038/ng0497-356. PMID 9090379.
- ^ Chu EC, Tarnawski AS (October 2004). "PTEN regulatory functions in tumor suppression and cell biology". Med. Sci. Monit. 10 (10): RA235–41. PMID 15448614.
- ^ "Entrez Gene: PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1)".
- ^ "OrthoMaM phylogenetic marker: PTEN coding sequence".
- ^ Chen Z, Trotman LC, Shaffer D, Lin HK, Dotan ZA, Niki M, Koutcher JA, Scher HI, Ludwig T, Gerald W, Cordon-Cardo C, Pandolfi PP (August 2005). "Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis". Nature 436 (7051): 725–30. doi:10.1038/nature03918. PMC 1939938. PMID 16079851.
- ^ a b c Pilarski R, Eng C (2004). "Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome". J Med Genet 41 (5): 323–6. doi:10.1136/jmg.2004.018036. PMC 1735782. PMID 15121767.
- ^ a b Napoli E, Ross-Inta C, Wong S, Hung C, Fujisawa Y, Sakaguchi D, Angelastro J, Omanska-Klusek A, Schoenfeld R, Giulivi C (2012). Bai, Yidong, ed. "Mitochondrial Dysfunction in Pten Haplo-Insufficient Mice with Social Deficits and Repetitive Behavior: Interplay between Pten and p53". PLoS ONE 7 (8): e42504. doi:10.1371/journal.pone.0042504. PMC 3416855. PMID 22900024.
- ^ "Rodent of the Week: Nerves regenerated after spinal cord injury". The Los Angeles Times. August 13, 2010.
- ^ Liu K, Lu Y, Lee JK, Samara R, Willenberg R, Sears-Kraxberger I, Tedeschi A, Park KK, Jin D, Cai B, Xu B, Connolly L, Steward O, Zheng B, He Z (September 2010). "PTEN deletion enhances the regenerative ability of adult corticospinal neurons". Nat. Neurosci. 13 (9): 1075–81. doi:10.1038/nn.2603. PMC 2928871. PMID 20694004.
- ^ a b 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 (March 1997). "PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer". Science 275 (5308): 1943–7. doi:10.1126/science.275.5308.1943. PMID 9072974.
- ^ a b Miller SJ, Lou David Y, Seldin David C, Lane William S, Neel Benjamin G (Sep 2002). "Direct identification of PTEN phosphorylation sites". FEBS Lett. 528 (1–3): 145–53. doi:10.1016/S0014-5793(02)03274-X. PMID 12297295.
- ^ Wu Y, Dowbenko D, Spencer S, Laura R, Lee J, Gu Q, Lasky L A (Jul 2000). "Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase". J. Biol. Chem. 275 (28): 21477–85. doi:10.1074/jbc.M909741199. PMID 10748157.
- ^ Yu Z, Fotouhi-Ardakani Nasser, Wu Liangtang, Maoui Meryem, Wang Shenglong, Banville Denis, Shen Shi-Hsiang (Oct 2002). "PTEN associates with the vault particles in HeLa cells". J. Biol. Chem. 277 (43): 40247–52. doi:10.1074/jbc.M207608200. PMID 12177006.
- ^ Wang X, Shi Yuji, Wang Junru, Huang Guochang, Jiang Xuejun (Sep 2008). "Crucial role of the C-terminus of PTEN in antagonizing NEDD4-1-mediated PTEN ubiquitination and degradation". Biochem. J. 414 (2): 221–9. doi:10.1042/BJ20080674. PMID 18498243.
- ^ Lin H-K, Hu Yueh-Chiang, Lee Dong Kun, Chang Chawnshang (Oct 2004). "Regulation of androgen receptor signaling by PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumor suppressor through distinct mechanisms in prostate cancer cells". Mol. Endocrinol. 18 (10): 2409–23. doi:10.1210/me.2004-0117. PMID 15205473.
- ^ Freeman DJ, Li Andrew G, Wei Gang, Li Heng-Hong, Kertesz Nathalie, Lesche Ralf, Whale Andrew D, Martinez-Diaz Hilda, Rozengurt Nora, Cardiff Robert D, Liu Xuan, Wu Hong (Feb 2003). "PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms". Cancer Cell 3 (2): 117–30. doi:10.1016/S1535-6108(03)00021-7. PMID 12620407.
- ^ Tamura M, Gu J, Danen E H, Takino T, Miyamoto S, Yamada K M (Jul 1999). "PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway". J. Biol. Chem. 274 (29): 20693–703. doi:10.1074/jbc.274.29.20693. PMID 10400703.
- ^ Haier Jö, Nicolson Garth L (Feb 2002). "PTEN regulates tumor cell adhesion of colon carcinoma cells under dynamic conditions of fluid flow". Oncogene 21 (9): 1450–60. doi:10.1038/sj.onc.1205213. PMID 11857088.
Further reading
- 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 (1997). "PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer". Science 275 (5308): 1943–1947. doi:10.1126/science.275.5308.1943. PMID 9072974.
- Simpson L, Parsons R (2001). "PTEN: life as a tumor suppressor". Exp Cell Res 264 (1): 29–41. doi:10.1006/excr.2000.5130. PMID 11237521.
- Chu EC, Tarnawski AS (2004). "PTEN regulatory functions in tumor suppression and cell biology". Med Sci Monit 10 (10): RA235–41. PMID 15448614.
- Eng C (2003). "PTEN: one gene, many syndromes". Hum Mutat 22 (3): 183–98. doi:10.1002/humu.10257. PMID 12938083.
- Hamada K, Sasaki T, Koni PA, Natsui M, Kishimoto H, Sasaki J, Yajima N, Horie Y, Hasegawa G, Naito M, Miyazaki J, Suda T, Itoh H, Nakao K, Mak TW, Nakano T, Suzuki A (2005). "The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis". Genes Dev 19 (17): 2054–65. doi:10.1101/gad.1308805. PMC 1199575. PMID 16107612.
- Leslie NR, Downes CP (2004). "PTEN function: how normal cells control it and tumour cells lose it". Biochem J 382 (Pt 1): 1–11. doi:10.1042/BJ20040825. PMC 1133909. PMID 15193142.
- Sansal I, Sellers WR (2004). "The biology and clinical relevance of the PTEN tumor suppressor pathway". J Clin Oncol 22 (14): 2954–63. doi:10.1200/JCO.2004.02.141. PMID 15254063.
- Waite KA, Eng C (2002). "Protean PTEN: Form and Function". Am J Hum Genet 70 (4): 829–44. doi:10.1086/340026. PMC 379112. PMID 11875759.
- Zhou XP, Waite KA, Pilarski R, Hampel H, Fernandez MJ, Bos C, Dasouki M, Feldman GL, Greenberg LA, Ivanovich J, Matloff E, Patterson A, Pierpont ME, Russo D, Nassif NT, Eng C (2003). "Germline PTEN Promoter Mutations and Deletions in Cowden/Bannayan-Riley-Ruvalcaba Syndrome Result in Aberrant PTEN Protein and Dysregulation of the Phosphoinositol-3-Kinase/Akt Pathway". Am J Hum Genet 73 (2): 404–11. doi:10.1086/377109. PMC 1180378. PMID 12844284.
- Ji S-P, Zhang Y, Cleemput JV, Jiang W, Liao M, Li L, Wan Q, Backstrom JR, Zhang X (2006). "Disruption of PTEN coupling with 5-HT2C receptors suppresses behavioral responses induced by drugs of abuse". Nature Medicine 12 (3): 324–9. doi:10.1038/nm1349. PMID 16474401.
External links
- GeneReviews/NCBI/NIH/UW entry on PTEN Hamartoma Tumor Syndrome (PHTS)
- PTEN Protein at the US National Library of Medicine Medical Subject Headings (MeSH)
- UMich Orientation of Proteins in Membranes protein/pdbid-1d5r
- "PTEN Gene - phosphatase and tensin homolog". GeneCards. The Weizmann Institute of Science. Retrieved 2009-03-12.
- "Gene overview of all published AD-association studies for PTEN". Alzforum: AlzGene. Alzheimer Research Forum. Retrieved 2009-03-12.
- Research shows gene defect's role in autism-like behavior
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
PDB gallery
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1d5r: Crystal Structure of the PTEN Tumor Suppressor
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Hydrolase: esterases (EC 3.1)
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3.1.1: Carboxylic ester hydrolases |
- Cholinesterase
- Acetylcholinesterase
- Butyrylcholinesterase
- Pectinesterase
- 6-phosphogluconolactonase
- PAF acetylhydrolase
- Lipase
- Bile salt-dependent
- Gastric/Lingual
- Pancreatic
- Lysosomal
- Hormone-sensitive
- Endothelial
- Hepatic
- Lipoprotein
- Monoacylglycerol
- Diacylglycerol
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3.1.2: Thioesterase |
- Palmitoyl protein thioesterase
- Ubiquitin carboxy-terminal hydrolase L1
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3.1.3: Phosphatase |
- Alkaline phosphatase
- Acid phosphatase (Prostatic)/Tartrate-resistant acid phosphatase/Purple acid phosphatases
- Nucleotidase
- Glucose 6-phosphatase
- Fructose 1,6-bisphosphatase
- Phosphoprotein phosphatase
- OCRL
- Pyruvate dehydrogenase phosphatase
- Fructose 6-P,2-kinase:fructose 2,6-bisphosphatase
- PTEN
- Phytase
- Inositol-phosphate phosphatase
- Phosphoprotein phosphatase: Protein tyrosine phosphatase
- Protein serine/threonine phosphatase
- Dual-specificity phosphatase
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3.1.4: Phosphodiesterase |
- Autotaxin
- Phospholipase
- Sphingomyelin phosphodiesterase
- PDE1
- PDE2
- PDE3
- PDE4A/PDE4B
- PDE5
- Lecithinase (Clostridium perfringens alpha toxin)
- Cyclic nucleotide phosphodiesterase
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3.1.6: Sulfatase |
- arylsulfatase
- Arylsulfatase A
- Arylsulfatase B
- Arylsulfatase E
- Steroid sulfatase
- Galactosamine-6 sulfatase
- Iduronate-2-sulfatase
- N-acetylglucosamine-6-sulfatase
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Nuclease (includes
deoxyribonuclease and
ribonuclease) |
3.1.11-16: Exonuclease |
Exodeoxyribonuclease |
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Exoribonuclease |
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3.1.21-31: Endonuclease |
Endodeoxyribonuclease |
- Deoxyribonuclease I
- Deoxyribonuclease II
- Deoxyribonuclease IV
- Restriction enzyme
- UvrABC endonuclease
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Endoribonuclease |
- RNase III
- RNase H
- RNase P
- RNase A
- RNase T1
- RNA-induced silencing complex
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either deoxy- or ribo- |
- Aspergillus nuclease S1
- Micrococcal nuclease
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- B
- enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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Neoplasm: Tumor suppressor genes/proteins and Oncogenes/Proto-oncogenes
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Ligand |
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Receptor |
Wnt signaling pathway
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Hedgehog signaling pathway
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TGF beta signaling pathway
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Receptor tyrosine kinase
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- ONCO: ErbB/c-ErbB
- c-Met
- c-Ret
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JAK-STAT signaling pathway
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Intracellular signaling P+Ps |
Wnt signaling pathway
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- ONCO: Beta-catenin
- TSP: APC
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TGF beta signaling pathway
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Akt/PKB signaling pathway
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Hippo signaling pathway
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TSP: Neurofibromin 2/Merlin
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MAPK/ERK pathway
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- TSP: Neurofibromin 1
- ONCO: c-Ras
- HRAS
- c-Raf
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Other/unknown
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Nucleus |
Cell cycle
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- TSP: p53
- pRb
- WT1
- p16/p14arf
- ONCO: CDK4
- Cyclin D
- Cyclin E
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DNA repair/Fanconi
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Ubiquitin ligase
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Transcription factor
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- TSP: KLF6
- ONCO: AP-1
- c-Myc
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Mitochondria |
- Apoptosis inhibitor: SDHB
- SDHD
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Other/ungrouped |
- c-Bcl-2 - Notch - Stathmin
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Description |
- Tumor suppressing and oncogenes
- Tumor markers
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Disease |
- Neoplasms and cancer
- Symptoms and signs
- Paraneoplastic
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Treatment |
- Drugs
- intracellular chemotherapeutics
- extracellular chemotherapeutics
- adjuvant detoxification
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