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Reviewed, UniProtKB/Swiss-Prot O08586 (PTEN_MOUSE)

Last modified January 19, 2010. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
    EC=3.1.3.67
    EC=3.1.3.16
    EC=3.1.3.48
Alternative name(s):
    Phosphatase and tensin homolog
    Mutated in multiple advanced cancers 1
Gene names
Name: Pten
Synonyms: Mmac1
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMus

Protein attributes

Sequence length403 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue By similarity. Ref.4

Catalytic activity

Phosphatidylinositol 3,4,5-trisphosphate + H2O = phosphatidylinositol 4,5-bisphosphate + phosphate.

A phosphoprotein + H2O = a protein + phosphate.

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Cofactor

Magnesium.

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 (via C2 domain) with FRK By similarity.

Subcellular location

Cytoplasm By similarity.

Post-translational modification

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 By similarity.

Sequence similarities

Contains 1 C2 tensin-type domain.

Contains 1 phosphatase tensin-type domain.

Ontologies

Keywords
   Biological processApoptosis
Lipid metabolism
   Cellular componentCytoplasm
   DiseaseTumor suppressor
   Molecular functionHydrolase
Protein phosphatase
   PTMAcetylation
Phosphoprotein
Gene Ontology (GO)
   Biological processangiogenesis

Inferred from mutant phenotype. Source: MGI

apoptosis

Inferred from electronic annotation. Source: UniProtKB-KW

cardiac muscle tissue development

Inferred from mutant phenotype. Source: MGI

central nervous system development

Inferred from mutant phenotype. Source: MGI

endothelial cell migration

Inferred from mutant phenotype. Source: MGI

induction of apoptosis

Inferred from mutant phenotype. Source: MGI

inositol phosphate dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptosis Ref.4

Inferred from mutant phenotype. Source: UniProtKB

negative regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of epithelial cell proliferation

Inferred from mutant phenotype. Source: MGI

negative regulation of focal adhesion assembly

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of protein kinase B signaling cascade Ref.4

Inferred from mutant phenotype. Source: UniProtKB

phosphoinositide dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

prostate gland growth

Inferred from mutant phenotype. Source: MGI

protein amino acid dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of B cell apoptosis

Inferred from mutant phenotype. Source: MGI

regulation of cell cycle

Inferred from genetic interaction. Source: MGI

regulation of myeloid cell apoptosis

Inferred from mutant phenotype. Source: MGI

regulation of protein stability

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular componentnucleus

Inferred from direct assay. Source: MGI

   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...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Cenpc1P494521EBI-1186266,EBI-1186252
PTENP604841EBI-1186266,EBI-696162From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 403403Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
PRO_0000215905

Regions

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

Sites

Active site1241Phosphocysteine intermediate Potential

Amino acid modifications

Modified residue61N6-acetyllysine By similarity
Modified residue3361Phosphotyrosine; by FRK By similarity
Modified residue3661Phosphothreonine By similarity
Modified residue3701Phosphoserine; by CK2 By similarity
Modified residue3851Phosphoserine; by CK2 By similarity
Modified residue4011Phosphothreonine By similarity

Experimental info

Sequence conflict501Missing in BAE28651. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O08586-1 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: 75F97C3DD6843BA9

FASTA40347,152
        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 PFDEDQHSQI TKV 

« Hide

References

« Hide 'large scale' 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: 9090379] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
Tissue: Sympathetic ganglion, Testis and Thymus.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: Czech II.
Tissue: Mammary gland.
[4]"PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway."
Sun H., Lesche R., Li D.M., Liliental J., Zhang H., Gao J., Gavrilova N., Mueller B., Liu X., Wu H.
Proc. Natl. Acad. Sci. U.S.A. 96:6199-6204(1999) [PubMed: 10339565] [Abstract]
Cited for: FUNCTION.
[5]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370 AND SER-385, MASS SPECTROMETRY.
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U92437 mRNA. Translation: AAC53118.1.
AK076980 mRNA. Translation: BAC36545.1.
AK088717 mRNA. Translation: BAC40525.1.
AK148736 mRNA. Translation: BAE28651.1.
BC021445 mRNA. Translation: AAH21445.1.
IPIIPI00114410.
RefSeqNP_032986.1.
UniGeneMm.245395

3D structure databases

SMRO08586. Positions 14-351.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-38740N.
IntActO08586. 3 interactions.
STRINGO08586.

PTM databases

PhosphoSiteO08586.

Proteomic databases

PRIDEO08586.

Genome annotation databases

EnsemblENSMUST00000013807; ENSMUSP00000013807; ENSMUSG00000013663; Mus musculus. [Genome view]
GeneID19211.
KEGGmmu:19211.
UCSCuc008hfr.1. mouse.

Organism-specific databases

CTD19211.
MGIMGI:109583. Pten.

Phylogenomic databases

eggNOGroNOG17599.
HOGENOMHBG745257.
HOVERGENO08586.
InParanoidO08586.
OMAERSDNDK.
OrthoDBEOG908QTZ.
PhylomeDBO08586.

Enzyme and pathway databases

BRENDA3.1.3.67. 244.

Gene expression databases

ArrayExpressO08586.
BgeeO08586.
CleanExMM_PTEN.
GenevestigatorO08586.
GermOnlineENSMUSG00000013663. Mus musculus.

Family and domain databases

InterProIPR017361. 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.
[Graphical view]
PfamPF00782. DSPc. 1 hit.
PF10409. PTEN_C2. 1 hit.
[Graphical view]
PIRSFPIRSF038025. PTEN. 1 hit.
PROSITEPS51182. C2_TENSIN. 1 hit.
PS51181. PPASE_TENSIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio295956.
SOURCESearch...

Entry information

Entry namePTEN_MOUSE
AccessionPrimary (citable) accession number: O08586
Secondary accession number(s): Q3UFB0, Q542G1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: January 19, 2010
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents