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Protein

Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN

Gene

PTEN

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement (By similarity).By similarity

Catalytic activityi

Phosphatidylinositol 3,4,5-trisphosphate + H2O = phosphatidylinositol 4,5-bisphosphate + phosphate.
[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.
Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei124Phosphocysteine intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Apoptosis, Lipid metabolism, Neurogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (EC:3.1.3.16, EC:3.1.3.48, EC:3.1.3.67)
Alternative name(s):
Mutated in multiple advanced cancers 1
Phosphatase and tensin homolog
Gene namesi
Name:PTEN
Synonyms:MMAC1
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Unplaced

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity
  • NucleusPML body By similarity

  • Note: Monoubiquitinated form is nuclear (By similarity). Nonubiquitinated form is cytoplasmic. Colocalized with PML and USP7 in PML nuclear bodies. XIAP/BIRC4 promotes its nuclear localization (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002159032 – 403Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENAdd BLAST402

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonineBy similarity1
Cross-linki13Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei294PhosphoserineBy similarity1
Modified residuei336Phosphotyrosine; by FRKBy similarity1
Modified residuei366Phosphothreonine; by GSK3-beta and PLK3By similarity1
Modified residuei370Phosphoserine; by CK2 and PLK3By similarity1
Modified residuei380Phosphoserine; by ROCK1By similarity1
Modified residuei382Phosphothreonine; by ROCK1By similarity1
Modified residuei383Phosphothreonine; by ROCK1By similarity1
Modified residuei385Phosphoserine; by CK2By similarity1
Modified residuei401PhosphothreonineBy similarity1

Post-translational modificationi

Constitutively phosphorylated by CK2 under normal conditions. Phosphorylation results in an inhibited activity towards PIP3. Phosphorylation can both inhibit or promote PDZ-binding. Phosphorylation at Tyr-336 by FRK/PTK5 protects this protein from ubiquitin-mediated degradation probably by inhibiting its binding to NEDD4. Phosphorylation by ROCK1 is essential for its stability and activity. Phosphorylation by PLK3 promotes its stability and prevents its degradation by the proteasome (By similarity).By similarity
Monoubiquitinated; monoubiquitination is increased in presence of retinoic acid. Deubiquitinated by USP7; leading to its nuclear exclusion. Monoubiquitination of one of either Lys-13 and Lys-289 amino acid is sufficient to modulate PTEN compartmentalization (By similarity). Ubiquitinated by XIAP/BIRC4 (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP60483.

Interactioni

Subunit structurei

Monomer. The unphosphorylated form interacts with the second PDZ domain of AIP1. Interacts with MAGI2, MAGI3, MAST1 and MAST3, but neither with MAST4 nor with DLG5; interaction with MAGI2 increases protein stability (By similarity). Interacts with NEDD4. Interacts with NDFIP1 and NDFIP2; in the presence of NEDD4 or ITCH, this interaction promotes PTEN ubiquitination (By similarity). Interacts (via C2 domain) with FRK (By similarity). Interacts with USP7; the interaction is direct (By similarity). Interacts with ROCK1 (By similarity). Interacts with XIAP/BIRC4 (By similarity). Interacts with STK11; the interaction phosphorylates PTEN (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

MINTiMINT-128368.
STRINGi9615.ENSCAFP00000023027.

Structurei

3D structure databases

ProteinModelPortaliP60483.
SMRiP60483.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 185Phosphatase tensin-typePROSITE-ProRule annotationAdd BLAST172
Domaini190 – 350C2 tensin-typePROSITE-ProRule annotationAdd BLAST161

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni401 – 403PDZ domain-bindingBy similarity3

Sequence similaritiesi

Contains 1 C2 tensin-type domain.PROSITE-ProRule annotation
Contains 1 phosphatase tensin-type domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2283. Eukaryota.
COG2453. LUCA.
HOGENOMiHOG000008008.
HOVERGENiHBG000239.
InParanoidiP60483.
KOiK01110.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR017361. Bifunc_PIno_P3_Pase/Pase_PTEN.
IPR000008. C2_dom.
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR014020. Tensin_C2-dom.
IPR029023. Tensin_lipid_phosphatase_dom.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
[Graphical view]
PfamiPF00782. DSPc. 1 hit.
PF10409. PTEN_C2. 1 hit.
[Graphical view]
PIRSFiPIRSF038025. PTEN. 1 hit.
SMARTiSM01326. PTEN_C2. 1 hit.
SM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF52799. SSF52799. 1 hit.
PROSITEiPS51182. C2_TENSIN. 1 hit.
PS51181. PPASE_TENSIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P60483-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTAIIKEIVS RNKRRYQEDG FDLDLTYIYP NIIAMGFPAE RLEGVYRNNI
60 70 80 90 100
DDVVRFLDSK HKNHYKIYNL CAERHYDTAK FNCRVAQYPF EDHNPPQLEL
110 120 130 140 150
IKPFCEDLDQ WLSEDDNHVA AIHCKAGKGR TGVMICAYLL HRGKFLKAQE
160 170 180 190 200
ALDFYGEVRT RDKKGVTIPS QRRYVYYYSY LLKNHLDYRP VALLFHKMMF
210 220 230 240 250
ETIPMFSGGT CNPQFVVCQL KVKIYSSNSG PTRREDKFMY FEFPQPLPVC
260 270 280 290 300
GDIKVEFFHK QNKMLKKDKM FHFWVNTFFI PGPEETSEKV ENGSLCDQEI
310 320 330 340 350
DSICSIERAD NDKEYLVLTL TKNDLDKANK DKANRYFSPN FKVKLYFTKT
360 370 380 390 400
VEEPSNPEAS SSTSVTPDVS DNEPDHYRYS DTTDSDPENE PFDEDQHTQI

TKV
Length:403
Mass (Da):47,166
Last modified:February 16, 2004 - v1
Checksum:i75F97C3DD6802BA9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U92435 mRNA. Translation: AAC48709.1.
RefSeqiNP_001003192.1. NM_001003192.1.
UniGeneiCfa.3695.

Genome annotation databases

GeneIDi403832.
KEGGicfa:403832.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U92435 mRNA. Translation: AAC48709.1.
RefSeqiNP_001003192.1. NM_001003192.1.
UniGeneiCfa.3695.

3D structure databases

ProteinModelPortaliP60483.
SMRiP60483.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-128368.
STRINGi9615.ENSCAFP00000023027.

Proteomic databases

PaxDbiP60483.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi403832.
KEGGicfa:403832.

Organism-specific databases

CTDi5728.

Phylogenomic databases

eggNOGiKOG2283. Eukaryota.
COG2453. LUCA.
HOGENOMiHOG000008008.
HOVERGENiHBG000239.
InParanoidiP60483.
KOiK01110.

Family and domain databases

Gene3Di3.90.190.10. 1 hit.
InterProiIPR017361. Bifunc_PIno_P3_Pase/Pase_PTEN.
IPR000008. C2_dom.
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR014020. Tensin_C2-dom.
IPR029023. Tensin_lipid_phosphatase_dom.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
[Graphical view]
PfamiPF00782. DSPc. 1 hit.
PF10409. PTEN_C2. 1 hit.
[Graphical view]
PIRSFiPIRSF038025. PTEN. 1 hit.
SMARTiSM01326. PTEN_C2. 1 hit.
SM00404. PTPc_motif. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF52799. SSF52799. 1 hit.
PROSITEiPS51182. C2_TENSIN. 1 hit.
PS51181. PPASE_TENSIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPTEN_CANLF
AccessioniPrimary (citable) accession number: P60483
Secondary accession number(s): O00633, O02679
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 16, 2004
Last sequence update: February 16, 2004
Last modified: November 2, 2016
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.