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P60483 (PTEN_CANFA) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:PTEN
Synonyms:MMAC1
OrganismCanis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]
Taxonomic identifier9615 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis

Protein attributes

Sequence length403 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

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.

Cofactor

Magnesium By similarity.

Subunit structure

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.

Subcellular location

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.

Post-translational modification

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.

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.

Sequence similarities

Contains 1 C2 tensin-type domain.

Contains 1 phosphatase tensin-type domain.

Ontologies

Keywords
   Biological processApoptosis
Lipid metabolism
Neurogenesis
   Cellular componentCytoplasm
Nucleus
   DiseaseTumor suppressor
   Molecular functionHydrolase
Protein phosphatase
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

central nervous system development

Inferred from sequence or structural similarity. Source: UniProtKB

heart development

Inferred from sequence or structural similarity. Source: UniProtKB

inositol phosphate dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of focal adhesion assembly

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of protein kinase B signaling

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine dephosphorylation

Inferred from sequence or structural similarity. Source: GOC

phosphatidylinositol dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase B signaling

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of protein stability

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentPML body

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionPDZ domain binding

Inferred from sequence or structural similarity. Source: UniProtKB

inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

magnesium ion binding

Inferred from electronic annotation. Source: InterPro

phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-3-phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein tyrosine phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein tyrosine/serine/threonine phosphatase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 403402Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
PRO_0000215903

Regions

Domain14 – 185172Phosphatase tensin-type
Domain190 – 350161C2 tensin-type
Region401 – 4033PDZ domain-binding By similarity

Sites

Active site1241Phosphocysteine intermediate Potential

Amino acid modifications

Modified residue21N-acetylthreonine By similarity
Modified residue3361Phosphotyrosine; by FRK By similarity
Modified residue3661Phosphothreonine; by GSK3-beta and PLK3 By similarity
Modified residue3701Phosphoserine; by CK2 and PLK3 By similarity
Modified residue3801Phosphoserine; by ROCK1 By similarity
Modified residue3821Phosphothreonine; by ROCK1 By similarity
Modified residue3831Phosphothreonine; by ROCK1 By similarity
Modified residue3851Phosphoserine; by CK2 By similarity
Modified residue4011Phosphothreonine By similarity
Cross-link13Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Sequences

Sequence LengthMass (Da)Tools
P60483 [UniParc].

Last modified February 16, 2004. Version 1.
Checksum: 75F97C3DD6802BA9

FASTA40347,166
        10         20         30         40         50         60 
MTAIIKEIVS RNKRRYQEDG FDLDLTYIYP NIIAMGFPAE RLEGVYRNNI DDVVRFLDSK 

        70         80         90        100        110        120 
HKNHYKIYNL CAERHYDTAK FNCRVAQYPF EDHNPPQLEL IKPFCEDLDQ WLSEDDNHVA 

       130        140        150        160        170        180 
AIHCKAGKGR TGVMICAYLL HRGKFLKAQE ALDFYGEVRT RDKKGVTIPS QRRYVYYYSY 

       190        200        210        220        230        240 
LLKNHLDYRP VALLFHKMMF ETIPMFSGGT CNPQFVVCQL KVKIYSSNSG PTRREDKFMY 

       250        260        270        280        290        300 
FEFPQPLPVC GDIKVEFFHK QNKMLKKDKM FHFWVNTFFI PGPEETSEKV ENGSLCDQEI 

       310        320        330        340        350        360 
DSICSIERAD NDKEYLVLTL TKNDLDKANK DKANRYFSPN FKVKLYFTKT VEEPSNPEAS 

       370        380        390        400 
SSTSVTPDVS DNEPDHYRYS DTTDSDPENE PFDEDQHTQI TKV 

« Hide

References

[1]"Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers."
Steck P.A., Pershouse M.A., Jasser S.A., Lin H., Yung W.K.A., Ligon A.H., Langford L.A., Baumgard M.L., Hattier T., Davis T., Frye C., Hu R., Swedlund B., Teng D.H.-F., Tavtigian S.V.
Nat. Genet. 15:356-363(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U92435 mRNA. Translation: AAC48709.1.
RefSeqNP_001003192.1. NM_001003192.1.
UniGeneCfa.3695.

3D structure databases

ProteinModelPortalP60483.
SMRP60483. Positions 14-351.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-128368.

Proteomic databases

PRIDEP60483.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID403832.
KEGGcfa:403832.

Organism-specific databases

CTD5728.

Phylogenomic databases

eggNOGCOG2453.
HOGENOMHOG000008008.
HOVERGENHBG000239.
InParanoidP60483.
KOK01110.

Family and domain databases

Gene3D3.90.190.10. 1 hit.
InterProIPR017361. 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.
[Graphical view]
PfamPF00782. DSPc. 1 hit.
PF10409. PTEN_C2. 1 hit.
[Graphical view]
PIRSFPIRSF038025. PTEN. 1 hit.
SUPFAMSSF49562. SSF49562. 1 hit.
SSF52799. SSF52799. 1 hit.
PROSITEPS51182. C2_TENSIN. 1 hit.
PS51181. PPASE_TENSIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio20817328.

Entry information

Entry namePTEN_CANFA
AccessionPrimary (citable) accession number: P60483
Secondary accession number(s): O00633, O02679
Entry history
Integrated into UniProtKB/Swiss-Prot: February 16, 2004
Last sequence update: February 16, 2004
Last modified: June 11, 2014
This is version 88 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families