EPS-HOS-00056
Eukaryotic Protein Kinase & Protein Phosphatase Database
TagContent
EKPD IDEPS-HOS-00056
Classification
Group/FamilyScoreE-ValueStartEndDomain Length
DSP/PTEN300.82.2E-8914185172
StatusReviewed
Ensembl ProteinENSP00000361021
UniProt AccessionP60484; B2R904; O00633; O02679; Q6ICT7;
Protein NamePhosphatidylinositol 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 NamePTEN
Gene Synonyms/Alias PTEN; MMAC1, TEP1;
Ensembl Information
Ensembl Gene IDEnsembl Protein IDEnsembl Transcript ID
ENSG00000171862ENSP00000361021ENST00000371953
OrganismHomo sapiens
Functional DescriptionTumor suppressor. Acts as a dual-specificity proteinphosphatase, 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.
Protein Length403
Protein Sequence
(FASTA)
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
Nucleotide Sequence
(FASTA)
ATGACAGCCA TCATCAAAGA GATCGTTAGC AGAAACAAAA GGAGATATCA AGAGGATGGA 60
TTCGACTTAG ACTTGACCTA TATTTATCCA AACATTATTG CTATGGGATT TCCTGCAGAA 120
AGACTTGAAG GCGTATACAG GAACAATATT GATGATGTAG TAAGGTTTTT GGATTCAAAG 180
CATAAAAACC ATTACAAGAT ATACAATCTT TGTGCTGAAA GACATTATGA CACCGCCAAA 240
TTTAATTGCA GAGTTGCACA ATATCCTTTT GAAGACCATA ACCCACCACA GCTAGAACTT 300
ATCAAACCCT TTTGTGAAGA TCTTGACCAA TGGCTAAGTG AAGATGACAA TCATGTTGCA 360
GCAATTCACT GTAAAGCTGG AAAGGGACGA ACTGGTGTAA TGATATGTGC ATATTTATTA 420
CATCGGGGCA AATTTTTAAA GGCACAAGAG GCCCTAGATT TCTATGGGGA AGTAAGGACC 480
AGAGACAAAA AGGGAGTAAC TATTCCCAGT CAGAGGCGCT ATGTGTATTA TTATAGCTAC 540
CTGTTAAAGA ATCATCTGGA TTATAGACCA GTGGCACTGT TGTTTCACAA GATGATGTTT 600
GAAACTATTC CAATGTTCAG TGGCGGAACT TGCAATCCTC AGTTTGTGGT CTGCCAGCTA 660
AAGGTGAAGA TATATTCCTC CAATTCAGGA CCCACACGAC GGGAAGACAA GTTCATGTAC 720
TTTGAGTTCC CTCAGCCGTT ACCTGTGTGT GGTGATATCA AAGTAGAGTT CTTCCACAAA 780
CAGAACAAGA TGCTAAAAAA GGACAAAATG TTTCACTTTT GGGTAAATAC ATTCTTCATA 840
CCAGGACCAG AGGAAACCTC AGAAAAAGTA GAAAATGGAA GTCTATGTGA TCAAGAAATC 900
GATAGCATTT GCAGTATAGA GCGTGCAGAT AATGACAAGG AATATCTAGT ACTTACTTTA 960
ACAAAAAATG ATCTTGACAA AGCAAATAAA GACAAAGCCA ACCGATACTT TTCTCCAAAT 1020
TTTAAGGTGA AGCTGTACTT CACAAAAACA GTAGAGGAGC CGTCAAATCC AGAGGCTAGC 1080
AGTTCAACTT CTGTAACACC AGATGTTAGT GACAATGAAC CTGATCATTA TAGATATTCT 1140
GACACCACTG ACTCTGATCC AGAGAATGAA CCTTTTGATG AAGATCAGCA TACACAAATT 1200
ACAAAAGTCT GA 1212
Domain Profile
S: 1     rrltedgfdldltyvteriiavsfPaeareevyrnnlrevvrlldskhrnkyklynlcse  60
         rr++edgfdldlty++++iia++fPae+ e+vyrnn+++vvr+ldskh+n+yk+ynlc+e
Q: 14    RRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAE  73
         79**********************************************************
S: 61    rrydltklnakvaefgiedlnaPaleklvsickeldeWlseddenvvvlhckggkgrlGv  120
         r+yd++k+n++va++++ed+n+P+le ++++c++ld+Wlsedd++v+++hck+gkgr+Gv
Q: 74    RHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGV  133
         ************************************************************
S: 121   ivcayllaseisakadealdtfgerrtredkvagvkqPsqrryvsyfsqllkgs  174
         ++cayll++++++ka+eald++ge+rtr++k  gv++Psqrryv+y+s+llk++
Q: 134   MICAYLLHRGKFLKAQEALDFYGEVRTRDKK--GVTIPSQRRYVYYYSYLLKNH  185
         *******************************..******************986
Domain Sequence
(FASTA)
RRYQEDGFDL DLTYIYPNII AMGFPAERLE GVYRNNIDDV VRFLDSKHKN HYKIYNLCAE 60
RHYDTAKFNC RVAQYPFEDH NPPQLELIKP FCEDLDQWLS EDDNHVAAIH CKAGKGRTGV 120
MICAYLLHRG KFLKAQEALD FYGEVRTRDK KGVTIPSQRR YVYYYSYLLK NH 172
Keyword3D-structure; Acetylation; 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 SourceEnsembl
Orthology
Ortholog group
Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Choloepus hoffmanni"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Dipodomys ordii"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Erinaceus europaeus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tarsius syrichta"; ?>Tetraodon nigroviridis"; ?>Vicugna pacos"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>Schizosaccharomyces pombe"; ?>
EPS-AIM-00070
EPS-ANC-00070
EPS-BOT-00060
EPS-CAE-00090
EPS-CAJ-00060
EPS-CAF-00075
EPS-CAP-00056
EPS-CHH-00018
EPS-CII-00031
EPS-CIS-00020
EPS-DAR-00103
EPS-DIO-00023
EPS-DRM-00027
EPS-EQC-00058
EPS-ERE-00015
EPS-FEC-00070
EPS-GAM-00057
EPS-GAG-00064
EPS-GAA-00095
EPS-GOG-00071
EPS-ICT-00059
EPS-LAC-00074
EPS-LOA-00054
EPS-MAM-00059
EPS-MEG-00066
EPS-MOD-00058
EPS-MUM-00056
EPS-MYL-00058
EPS-NOL-00066
EPS-ORN-00073
EPS-ORA-00063
EPS-ORC-00054
EPS-ORL-00083
EPS-OTG-00058
EPS-PAT-00053
EPS-PES-00071
EPS-POA-00072
EPS-RAN-00059
EPS-SAH-00057
EPS-SUS-00058
EPS-TAG-00068
EPS-TAR-00092
EPS-TAS-00020
EPS-TEN-00069
EPS-VIP-00021
EPS-XET-00068
EPS-XIM-00102
EPS-SCP-00017
Gene Ontology
GO:0005829; C:cytosol
GO:0009898; C:internal side of plasma membrane
GO:0035749; C:myelin sheath adaxonal region
GO:0043005; C:neuron projection
GO:0005634; C:nucleus
GO:0016605; C:PML body
GO:0043220; C:Schmidt-Lanterman incisure
GO:0051717; F:inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity
GO:0008289; F:lipid binding
GO:0000287; F:magnesium ion binding
GO:0016314; F:phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity
GO:0051800; F:phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity
GO:0004438; F:phosphatidylinositol-3-phosphatase activity
GO:0004722; F:protein serine/threonine phosphatase activity
GO:0004725; F:protein tyrosine phosphatase activity
GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity
GO:0007092; P:activation of mitotic anaphase-promoting complex activity
GO:0001525; P:angiogenesis
GO:0006915; P:apoptotic process
GO:0060070; P:canonical Wnt receptor signaling pathway
GO:0048738; P:cardiac muscle tissue development
GO:0016477; P:cell migration
GO:0008283; P:cell proliferation
GO:0032286; P:central nervous system myelin maintenance
GO:0021955; P:central nervous system neuron axonogenesis
GO:0060997; P:dendritic spine morphogenesis
GO:0021542; P:dentate gyrus development
GO:0043542; P:endothelial cell migration
GO:0007173; P:epidermal growth factor receptor signaling pathway
GO:0008543; P:fibroblast growth factor receptor signaling pathway
GO:0048853; P:forebrain morphogenesis
GO:0007507; P:heart development
GO:0006917; P:induction of apoptosis
GO:0046855; P:inositol phosphate dephosphorylation
GO:0007611; P:learning or memory
GO:0045475; P:locomotor rhythm
GO:0060291; P:long-term synaptic potentiation
GO:0060179; P:male mating behavior
GO:0042711; P:maternal behavior
GO:0033555; P:multicellular organismal response to stress
GO:0043066; P:negative regulation of apoptotic process
GO:0050771; P:negative regulation of axonogenesis
GO:0090344; P:negative regulation of cell aging
GO:0030336; P:negative regulation of cell migration
GO:0008285; P:negative regulation of cell proliferation
GO:0045792; P:negative regulation of cell size
GO:0031658; P:negative regulation of cyclin-dependent protein kinase activity involved in G1/S
GO:0061002; P:negative regulation of dendritic spine morphogenesis
GO:0050680; P:negative regulation of epithelial cell proliferation
GO:0090394; P:negative regulation of excitatory postsynaptic membrane potential
GO:0051895; P:negative regulation of focal adhesion assembly
GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle
GO:0031642; P:negative regulation of myelination
GO:0046621; P:negative regulation of organ growth
GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase cascade
GO:0051898; P:negative regulation of protein kinase B signaling cascade
GO:0090071; P:negative regulation of ribosome biogenesis
GO:2000808; P:negative regulation of synaptic vesicle clustering
GO:0048011; P:nerve growth factor receptor signaling pathway
GO:0007270; P:neuron-neuron synaptic transmission
GO:0006661; P:phosphatidylinositol biosynthetic process
GO:0046856; P:phosphatidylinositol dephosphorylation
GO:0048015; P:phosphatidylinositol-mediated signaling
GO:0008284; P:positive regulation of cell proliferation
GO:2000463; P:positive regulation of excitatory postsynaptic membrane potential
GO:2000060; P:positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity
GO:0097107; P:postsynaptic density assembly
GO:0060134; P:prepulse inhibition
GO:0097105; P:presynaptic membrane assembly
GO:0060736; P:prostate gland growth
GO:0043491; P:protein kinase B signaling cascade
GO:0050821; P:protein stabilization
GO:0002902; P:regulation of B cell apoptotic process
GO:0033032; P:regulation of myeloid cell apoptotic process
GO:0060024; P:rhythmic synaptic transmission
GO:0035176; P:social behavior
GO:0060074; P:synapse maturation
GO:0050852; P:T cell receptor signaling pathway
KEGG
hsa:5728;
InterPros
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; 1.
PF10409; PTEN_C2; 1.
SMARTs
Prosites
PS51182; C2_TENSIN; 1.
PS51181; PPASE_TENSIN; 1.
Prints
Created Date20-Feb-2013