Reviewed, UniProtKB/Swiss-Prot O08586 (PTEN_MOUSE)

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	403 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Apoptosis Lipid metabolism
Cellular component	Cytoplasm
Disease	Tumor suppressor
Molecular function	Hydrolase Protein phosphatase
PTM	Acetylation Phosphoprotein
Gene Ontology (GO)
Biological process	angiogenesis 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 component	nucleus Inferred from direct assay. Source: MGI
Molecular function	PDZ 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
Cenpc1	P49452	1	EBI-1186266,EBI-1186252
PTEN	P60484	1	EBI-1186266,EBI-696162	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 403	403	Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN		PRO_0000215905
Regions
	Domain	14 – 185	172	Phosphatase tensin-type
	Domain	190 – 350	161	C2 tensin-type
	Region	401 – 403	3	PDZ domain-binding By similarity
Sites
	Active site	124	1	Phosphocysteine intermediate Potential
Amino acid modifications
	Modified residue	6	1	N6-acetyllysine By similarity
	Modified residue	336	1	Phosphotyrosine; by FRK By similarity
	Modified residue	366	1	Phosphothreonine By similarity
	Modified residue	370	1	Phosphoserine; by CK2 By similarity
	Modified residue	385	1	Phosphoserine; by CK2 By similarity
	Modified residue	401	1	Phosphothreonine By similarity
Experimental info
	Sequence conflict	50	1	Missing in BAE28651. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O08586-1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 75F97C3DD6843BA9	FASTA	403	47,152
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00114410.
RefSeq	NP_032986.1.
UniGene	Mm.245395
3D structure databases
SMR	O08586. Positions 14-351.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-38740N.
IntAct	O08586. 3 interactions.
STRING	O08586.
PTM databases
PhosphoSite	O08586.
Proteomic databases
PRIDE	O08586.
Genome annotation databases
Ensembl	ENSMUST00000013807; ENSMUSP00000013807; ENSMUSG00000013663; Mus musculus. [Genome view]
GeneID	19211.
KEGG	mmu:19211.
UCSC	uc008hfr.1. mouse.
Organism-specific databases
CTD	19211.
MGI	MGI:109583. Pten.
Phylogenomic databases
eggNOG	roNOG17599.
HOGENOM	HBG745257.
HOVERGEN	O08586.
InParanoid	O08586.
OMA	ERSDNDK.
OrthoDB	EOG908QTZ.
PhylomeDB	O08586.
Enzyme and pathway databases
BRENDA	3.1.3.67. 244.
Gene expression databases
ArrayExpress	O08586.
Bgee	O08586.
CleanEx	MM_PTEN.
Genevestigator	O08586.
GermOnline	ENSMUSG00000013663. Mus musculus.
Family and domain databases
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. [Graphical view]
Pfam	PF00782. DSPc. 1 hit. PF10409. PTEN_C2. 1 hit. [Graphical view]
PIRSF	PIRSF038025. PTEN. 1 hit.
PROSITE	PS51182. C2_TENSIN. 1 hit. PS51181. PPASE_TENSIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	295956.
SOURCE	Search...

Entry information

Entry name

PTEN_MOUSE

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)