PTEN (基因)

磷酸酯酶与张力蛋白同源物
人PTEN的晶体结构图。N-端磷酸酯酶结构域以蓝色表示而C-端C2结构域以红色表示[1]。
有效结构
PDB 直系同源检索：PDBe, RCSB
PDB查询代码列表

1D5R, 2KYL

标识
代号 PTEN; 10q23del; BZS; CWS1; DEC; GLM2; MHAM; MMAC1; PTEN1; TEP1
扩展标识 遗传学：601728 鼠基因：109583 同源基因：265 GeneCards: PTEN Gene
EC編號 3.1.3.16, 3.1.3.48, 3.1.3.67
基因本体论描述
分子功能 · magnesium ion binding

· phosphatidylinositol-3-phosphatase activity
· phosphoprotein phosphatase activity
· protein serine/threonine phosphatase activity
· protein tyrosine phosphatase activity
· 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
细胞成分 · nucleus

· cytoplasm
· cytosol
· plasma membrane
· internal side of plasma membrane
· PML body
· myelin sheath adaxonal region
· cell projection
· neuron projection

· Schmidt-Lanterman incisure
生物过程 · 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
· induction of apoptosis
· 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
· learning or memory
· locomotory behavior
· cell proliferation
· positive regulation of cell proliferation
· negative regulation of cell proliferation
· fibroblast growth factor receptor signaling pathway
· regulation of neuron projection development
· negative regulation of phosphatidylinositol 3-kinase cascade
· 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
· central nervous system myelin maintenance
· regulation of cellular component size
· regulation of myeloid cell apoptotic process
· multicellular organismal response to stress
· social behavior
· peptidyl-tyrosine dephosphorylation
· maternal behavior
· negative regulation of apoptotic process
· protein kinase B signaling cascade
· endothelial cell migration
· inositol phosphate metabolic process
· small molecule metabolic process
· innate immune response
· locomotor rhythm
· negative regulation of cell size
· negative regulation of organ growth
· inositol phosphate dephosphorylation
· phosphatidylinositol dephosphorylation
· 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 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 cascade
· rhythmic synaptic transmission
· canonical Wnt receptor signaling pathway
· synapse maturation
· prepulse inhibition
· male mating behavior
· long-term synaptic potentiation
· 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
Sources: Amigo / QuickGO
直系同源体
物种 人类 小鼠
Entrez 5728 19211
Ensembl ENSG00000171862 ENSMUSG00000013663
UniProt P60484 O08586
mRNA序列 NM_000314 NM_008960
蛋白序列 NP_000305 NP_032986
基因位置 Chr 10:
89.62 – 89.73 Mb		 Chr 19:
32.76 – 32.83 Mb
PubMed查询 [1] [2]
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磷酸酯酶与张力蛋白同源物（英語：Phosphatase and tensin homolog，简称为PTEN）是一种在人体中由PTEN基因编码的蛋白质[2]。该基因的突变是多种癌症进展过程的环节之一。

PTEN通过其磷酸酯酶蛋白产物而行使一种抑癌基因的作用。这一磷酸酯酶参与了细胞周期的调节，阻止细胞过快地生长与分裂[3]。其为癌微RNAMIRN21的靶之一。

该基因被鉴定为一种肿瘤抑制物，在多种癌症中往往处于变异状态。该基因编码的蛋白质是一种磷脂酰肌醇-3,4,5-三磷酸3-磷酸酯酶。该蛋白同时含有一张力蛋白样结构域及一催化结构域，这与双特异性蛋白酪氨酸磷酸酶很相似。但与大部分蛋白质酪氨酸磷酸酶不同的是，该蛋白偏好脱去磷酸肌醇底物上的磷酸。该蛋白负性调控胞内磷脂酰肌醇-3,4,5-三磷酸的水平，并通过负性调控Akt/PKB信号通道发挥抑癌基因的作用[4]。

參考文献

  1. ^ PDB 1d5r；Lee JO, Yang H, Georgescu MM, Di Cristofano A, Maehama T, Shi Y, Dixon JE, Pandolfi P, Pavletich NP. Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell. October 1999, 99 (3): 323–34. PMID 10555148. doi:10.1016/S0092-8674(00)81663-3. 
  2. ^ 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. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat. Genet. April 1997, 15 (4): 356–62. PMID 9090379. doi:10.1038/ng0497-356. 
  3. ^ Chu EC, Tarnawski AS. PTEN regulatory functions in tumor suppression and cell biology. Med. Sci. Monit. October 2004, 10 (10): RA235–41 [2013-05-25]. PMID 15448614. （原始内容存档于2012-02-14）. 
  4. ^ Entrez Gene: PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1). （原始内容存档于2010-03-07）. 

深入阅读

  • 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. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997, 275 (5308): 1943–1947. PMID 9072974. doi:10.1126/science.275.5308.1943. 
  • Simpson L, Parsons R. PTEN: life as a tumor suppressor. Exp Cell Res. 2001, 264 (1): 29–41. PMID 11237521. doi:10.1006/excr.2000.5130. 
  • Chu EC, Tarnawski AS. PTEN regulatory functions in tumor suppression and cell biology. Med Sci Monit. 2004, 10 (10): RA235–41. PMID 15448614. 
  • Eng C. PTEN: one gene, many syndromes. Hum Mutat. 2003, 22 (3): 183–98. PMID 12938083. doi:10.1002/humu.10257. 
  • 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. The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis. Genes Dev. 2005, 19 (17): 2054–65. PMC 1199575 可免费查阅. PMID 16107612. doi:10.1101/gad.1308805. 
  • Leslie NR, Downes CP. PTEN function: how normal cells control it and tumour cells lose it. Biochem J. 2004, 382 (Pt 1): 1–11. PMC 1133909 可免费查阅. PMID 15193142. doi:10.1042/BJ20040825. 
  • Pilarski R, Eng C. Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome. J Med Genet. 2004, 41 (5): 323–6. PMC 1735782 可免费查阅. PMID 15121767. doi:10.1136/jmg.2004.018036. 
  • Sansal I, Sellers WR. The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol. 2004, 22 (14): 2954–63. PMID 15254063. doi:10.1200/JCO.2004.02.141. 
  • Waite KA, Eng C. Protean PTEN: Form and Function. Am J Hum Genet. 2002, 70 (4): 829–44. PMC 379112 可免费查阅. PMID 11875759. doi:10.1086/340026. 
  • 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. 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. 2003, 73 (2): 404–11. PMC 1180378 可免费查阅. PMID 12844284. doi:10.1086/377109. 
  • Ji S-P, Zhang Y, Cleemput JV, Jiang W, Liao M, Li L, Wan Q, Backstrom JR, Zhang X. Disruption of PTEN coupling with 5-HT2C receptors suppresses behavioral responses induced by drugs of abuse. Nature Medicine. 2006, 12 (3): 324–9. PMID 16474401. doi:10.1038/nm1349. 

外部链接

  • GeneReviews/NCBI/NIH/UW entry on PTEN Hamartoma Tumor Syndrome (PHTS)（页面存档备份，存于互联网档案馆）
  • 醫學主題詞表（MeSH）：PTEN+Protein
  • Template:UMichOPM
  • PTEN Gene - phosphatase and tensin homolog. GeneCards. The Weizmann Institute of Science. [2009-03-12]. （原始内容存档于2007-10-08）. 
  • Gene overview of all published AD-association studies for PTEN. Alzforum: AlzGene. Alzheimer Research Forum. [2009-03-12]. （原始内容存档于2009-02-10）. 
  • Research shows gene defect's role in autism-like behavior

PTEN (基因)引用了美国国家医学图书馆提供的資料，这些資料属于公共领域。

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  • Template:PDB Gallery/5728

Template:蛋白酪氨酸磷酸酶类

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3.1.1：羧酸酯水解酶类
胆碱酯酶（乙酰胆碱酯酶、丁酰胆碱酯酶（英语：Butyrylcholinesterase）） · 果胶酯酶 · 6-磷酸葡萄糖酸内酯酶 · 血小板活化因子乙酰水解酶

脂酶（胆盐依赖性脂酶、胃脂肪酶/舌脂肪酶、胰脂肪酶、溶酶体酸性脂肪酶、激素敏感性脂肪酶、内皮脂肪酶、肝脂肪酶、脂蛋白脂肪酶、单酰基甘油脂肪酶、二酰基甘油脂肪酶）

磷脂酶（A1、A2、B）

角质酶（英语：Cutinase） · PET酶
3.1.2：硫酯水解酶类
泛素C末端水解酶更多见{{硫酯酶}}
磷酸酶
碱性磷酸酶（ALPI、ALPL、ALPP） · 酸性磷酸酶（前列腺酸性磷酸酶）/抗酒石酸酸性磷酸酶/紫色酸性磷酸酶 · 核苷酸酶 · 葡萄糖6-磷酸酶 · 果糖1,6-二磷酸酶 · 钙调磷酸酶 · 磷蛋白磷酸酯酶（PP2） · OCRL · 丙酮酸脱氢酶磷酸酶 · 磷酸果糖激酶2 · PTEN · 植酸酶 · 磷酸肌醇磷酸酶（IMPA1）
磷蛋白磷酸酶：蛋白酪氨酸磷酸酶 · 蛋白丝氨酸/苏氨酸磷酸酶 · 双特异性磷酸酶
自分泌运动因子 · 磷脂酶（磷脂酶C、磷脂酶D） · 鞘磷脂磷酸二酯酶（1) · PDE1 · PDE2 · PDE3 · PDE4A/PDE4B · PDE5 · 卵磷脂酶（产气荚膜梭菌α毒素） · 环核苷酸磷酸二酯酶
3.1.6：硫酸酯酶类
芳基硫酸酯酶（芳基硫酸酯酶A、芳基硫酸酯酶B、芳基硫酸酯酶E、类固醇硫酸酯酶） · 氨基半乳糖-6硫酸酯酶 · 艾杜糖醛酸-2-硫酸酯酶 · N-乙酰氨基葡萄糖-6-硫酸酯酶
核酸酶（包含
脱氧核糖核酸酶
及核糖核酸酶）
3.1.11-3.1.16：外切酶
寡核苷酸酶
3.1.21-3.1.31：内切酶
脱氧核糖核酸内切酶
  • 脱氧核糖核酸内切酶Ⅰ
  • 脱氧核糖核酸内切酶Ⅱ
  • 脱氧核糖核酸内切酶Ⅳ
  • 限制性内切酶更多见{{限制酶}}
  • UvrABC核酸内切酶
作用于脱氧核糖核酸或核糖核酸
  • 曲霉属核酸酶S1
  • 微球菌核酸酶
EC 1.1/2/3/4/5/6/7/8/9/10/11/12/13/14/15/16/17/18/19/20/21/22 · 2.1/2/3/4/5/6/7(2.7.10/11-12)/8/9 · 3.1/2/3/4(3.4.21/22/23/24)/5/6/7/8/9/10/11/12/13 · 4.1/2/3/4/5/6 · 5.1/2/3/4/5/99 · 6.1-3（英语：Template:Ligases CO CS and CN）/4/5-6
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配體
  • ONCO：c-Sis/PDGF
  • HGF
受体
  • TSP: CDH1
  • TSP：PTCH1
TGFβ信号通路
  • TSP: TGFβ受体2
  • ONCO：c-Kit
  • Flt3
胞内信号P+P
  • ONCO：β-联蛋白
  • TSP：APC
TGFβ信号通路
  • TSP：SMAD2
  • SMAD4
河马信号通路
TSP：神经纤维瘤蛋白2/膜突样蛋白
MAPK/ERK途径
  • TSP：神经纤维瘤蛋白1
  • ONCO：c-Ras
  • HRAS
  • c-Raf
其他/未知
  • TSP: Maspin
  • ONCO: c-Src
核
  • TSP：p53
  • pRb
  • WT1
  • p16/p14arf
  • ONCO：CDK4
  • 周期蛋白D
  • 周期蛋白E
DNA修复/范科尼
  • TSP：VHL
  • ONCO: CBL
  • MDM2
  • TSP: KLF6
  • ONCO: AP-1
    • c-Fos
    • c-Jun
  • c-Myc
线粒体
  • 凋亡抑制剂：SDHB
  • SDHD
其他/未分组
  • c-Bcl-2 - Notch - 抑微管装配蛋白

医学导航: 肿瘤

基因/标志

肿瘤/同名/附瘤

药物 (L1i/1e/V03)