CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-009211
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN 
Protein Synonyms/Alias
 Mutated in multiple advanced cancers 1; Phosphatase and tensin homolog 
Gene Name
 PTEN 
Gene Synonyms/Alias
 MMAC1; TEP1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
6**MTAIIKEIVSRNKacetylation[1]
6**MTAIIKEIVSRNKubiquitination[2]
13KEIVSRNKRRYQEDGubiquitination[3]
80ERHYDTAKFNCRVAQubiquitination[2]
125HVAAIHCKAGKGRTGacetylation[4]
128AIHCKAGKGRTGVMIacetylation[4]
289GPEETSEKVENGSLCubiquitination[3]
402DQHTQITKV******acetylation[5]
Reference
 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [4] PCAF modulates PTEN activity.
 Okumura K, Mendoza M, Bachoo RM, DePinho RA, Cavenee WK, Furnari FB.
 J Biol Chem. 2006 Sep 8;281(36):26562-8. [PMID: 16829519]
 [5] PTEN acetylation modulates its interaction with PDZ domain.
 Ikenoue T, Inoki K, Zhao B, Guan KL.
 Cancer Res. 2008 Sep 1;68(17):6908-12. [PMID: 18757404] 
Functional Description
 Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine- phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3- phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K- AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with AIP1 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability. 
Sequence Annotation
 DOMAIN 14 185 Phosphatase tensin-type.
 DOMAIN 190 350 C2 tensin-type.
 REGION 401 403 PDZ domain-binding.
 ACT_SITE 124 124 Phosphocysteine intermediate (Potential).
 MOD_RES 336 336 Phosphotyrosine; by FRK.
 MOD_RES 366 366 Phosphothreonine; by GSK3-beta and PLK3.
 MOD_RES 370 370 Phosphoserine; by CK2 and PLK3.
 MOD_RES 380 380 Phosphoserine; by ROCK1 and CK2.
 MOD_RES 382 382 Phosphothreonine; by ROCK1 and CK2.
 MOD_RES 383 383 Phosphothreonine; by ROCK1 and CK2.
 MOD_RES 385 385 Phosphoserine; by CK2.
 MOD_RES 401 401 Phosphothreonine.
 CROSSLNK 13 13 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 289 289 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Apoptosis; Complete proteome; Cytoplasm; Disease mutation; Hydrolase; Isopeptide bond; Lipid metabolism; Lipid-binding; Neurogenesis; Nucleus; Phosphoprotein; Polymorphism; Protein phosphatase; Reference proteome; Tumor suppressor; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 403 AA 
Protein Sequence
MTAIIKEIVS RNKRRYQEDG FDLDLTYIYP NIIAMGFPAE RLEGVYRNNI DDVVRFLDSK 60
HKNHYKIYNL CAERHYDTAK FNCRVAQYPF EDHNPPQLEL IKPFCEDLDQ WLSEDDNHVA 120
AIHCKAGKGR TGVMICAYLL HRGKFLKAQE ALDFYGEVRT RDKKGVTIPS QRRYVYYYSY 180
LLKNHLDYRP VALLFHKMMF ETIPMFSGGT CNPQFVVCQL KVKIYSSNSG PTRREDKFMY 240
FEFPQPLPVC GDIKVEFFHK QNKMLKKDKM FHFWVNTFFI PGPEETSEKV ENGSLCDQEI 300
DSICSIERAD NDKEYLVLTL TKNDLDKANK DKANRYFSPN FKVKLYFTKT VEEPSNPEAS 360
SSTSVTPDVS DNEPDHYRYS DTTDSDPENE PFDEDQHTQI TKV 403 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0009898; C:internal side of plasma membrane; IDA:UniProtKB.
 GO:0035749; C:myelin sheath adaxonal region; ISS:BHF-UCL.
 GO:0043005; C:neuron projection; ISS:BHF-UCL.
 GO:0005634; C:nucleus; IDA:BHF-UCL.
 GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
 GO:0043220; C:Schmidt-Lanterman incisure; ISS:BHF-UCL.
 GO:0051717; F:inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity; IDA:UniProtKB.
 GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
 GO:0000287; F:magnesium ion binding; IEA:InterPro.
 GO:0016314; F:phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity; IDA:UniProtKB.
 GO:0051800; F:phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity; IDA:UniProtKB.
 GO:0004438; F:phosphatidylinositol-3-phosphatase activity; IDA:UniProtKB.
 GO:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB.
 GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB.
 GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IEA:InterPro.
 GO:0007092; P:activation of mitotic anaphase-promoting complex activity; IDA:BHF-UCL.
 GO:0001525; P:angiogenesis; IEA:Compara.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0060070; P:canonical Wnt receptor signaling pathway; IDA:BHF-UCL.
 GO:0048738; P:cardiac muscle tissue development; IEA:Compara.
 GO:0016477; P:cell migration; ISS:UniProtKB.
 GO:0008283; P:cell proliferation; TAS:UniProtKB.
 GO:0032286; P:central nervous system myelin maintenance; ISS:BHF-UCL.
 GO:0021955; P:central nervous system neuron axonogenesis; ISS:BHF-UCL.
 GO:0060997; P:dendritic spine morphogenesis; ISS:BHF-UCL.
 GO:0021542; P:dentate gyrus development; ISS:BHF-UCL.
 GO:0043542; P:endothelial cell migration; IEA:Compara.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0048853; P:forebrain morphogenesis; ISS:BHF-UCL.
 GO:0007507; P:heart development; ISS:UniProtKB.
 GO:0006917; P:induction of apoptosis; ISS:UniProtKB.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0046855; P:inositol phosphate dephosphorylation; IDA:UniProtKB.
 GO:0007611; P:learning or memory; ISS:BHF-UCL.
 GO:0045475; P:locomotor rhythm; ISS:BHF-UCL.
 GO:0060291; P:long-term synaptic potentiation; IEA:Compara.
 GO:0060179; P:male mating behavior; IEA:Compara.
 GO:0042711; P:maternal behavior; IEA:Compara.
 GO:0033555; P:multicellular organismal response to stress; ISS:BHF-UCL.
 GO:0043066; P:negative regulation of apoptotic process; IEA:Compara.
 GO:0050771; P:negative regulation of axonogenesis; ISS:BHF-UCL.
 GO:0090344; P:negative regulation of cell aging; IEA:Compara.
 GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB.
 GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
 GO:0045792; P:negative regulation of cell size; ISS:BHF-UCL.
 GO:0031658; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle; IDA:BHF-UCL.
 GO:0061002; P:negative regulation of dendritic spine morphogenesis; ISS:BHF-UCL.
 GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Compara.
 GO:0090394; P:negative regulation of excitatory postsynaptic membrane potential; ISS:BHF-UCL.
 GO:0051895; P:negative regulation of focal adhesion assembly; IMP:UniProtKB.
 GO:0031642; P:negative regulation of myelination; IEA:Compara.
 GO:0046621; P:negative regulation of organ growth; ISS:BHF-UCL.
 GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase cascade; TAS:BHF-UCL.
 GO:0051898; P:negative regulation of protein kinase B signaling cascade; IMP:UniProtKB.
 GO:0090071; P:negative regulation of ribosome biogenesis; IEA:Compara.
 GO:2000808; P:negative regulation of synaptic vesicle clustering; ISS:BHF-UCL.
 GO:0007270; P:neuron-neuron synaptic transmission; ISS:BHF-UCL.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
 GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:UniProtKB.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:0008284; P:positive regulation of cell proliferation; ISS:BHF-UCL.
 GO:2000463; P:positive regulation of excitatory postsynaptic membrane potential; ISS:BHF-UCL.
 GO:2000060; P:positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
 GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IMP:BHF-UCL.
 GO:0097107; P:postsynaptic density assembly; ISS:BHF-UCL.
 GO:0060134; P:prepulse inhibition; ISS:BHF-UCL.
 GO:0097105; P:presynaptic membrane assembly; ISS:BHF-UCL.
 GO:0060736; P:prostate gland growth; IEA:Compara.
 GO:0043491; P:protein kinase B signaling cascade; ISS:UniProtKB.
 GO:0050821; P:protein stabilization; IDA:BHF-UCL.
 GO:0002902; P:regulation of B cell apoptotic process; IEA:Compara.
 GO:0033032; P:regulation of myeloid cell apoptotic process; IEA:Compara.
 GO:0060024; P:rhythmic synaptic transmission; ISS:BHF-UCL.
 GO:0035176; P:social behavior; ISS:BHF-UCL.
 GO:0060074; P:synapse maturation; ISS:BHF-UCL.
 GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome. 
Interpro
 IPR017361; Bifunc_PIno_P3_Pase/Pase_PTEN.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 IPR000340; Dual-sp_phosphatase_cat-dom.
 IPR014019; Phosphatase_tensin-typ.
 IPR014020; Tensin_phosphatase_C2-dom.
 IPR016130; Tyr_Pase_AS. 
Pfam
 PF00782; DSPc
 PF10409; PTEN_C2 
SMART
  
PROSITE
 PS51182; C2_TENSIN
 PS51181; PPASE_TENSIN 
PRINTS