Reviewed, UniProtKB/Swiss-Prot P60483 (PTEN_CANFA)

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

Canis familiaris (Dog)

Taxonomic identifier

9615 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis

Protein attributes

Sequence length	403 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue By similarity.
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 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 (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	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW central nervous system development Inferred from sequence or structural similarity. Source: UniProtKB induction of apoptosis 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 formation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein kinase B signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB phosphoinositide dephosphorylation Inferred from sequence or structural similarity. Source: UniProtKB protein amino acid dephosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of protein stability Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB
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...

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_0000215903
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

Sequences

	Sequence		Length	Mass (Da)
	P60483-1 [UniParc]. Last modified February 16, 2004. Version 1. Checksum: 75F97C3DD6802BA9	FASTA	403	47,166
	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

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].

Cross-references

Sequence databases
EMBL GenBank DDBJ	U92435 mRNA. Translation: AAC48709.1.
RefSeq	NP_001003192.1.
UniGene	Cfa.3695
3D structure databases
SMR	P60483. Positions 14-351.
ModBase	Search...
Protein-protein interaction databases
STRING	P60483.
Genome annotation databases
Ensembl	ENSCAFT00000024821; ENSCAFP00000023027; ENSCAFG00000015670; Canis familiaris. [Genome view]
GeneID	403832.
KEGG	cfa:403832.
Organism-specific databases
CTD	403832.
Phylogenomic databases
eggNOG	maNOG08348.
HOVERGEN	P60483.
InParanoid	P60483.
OrthoDB	EOG908QTZ.
Enzyme and pathway databases
BRENDA	3.1.3.67. 463.
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...

Entry information

Entry name

PTEN_CANFA

Accession

Primary (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:	January 19, 2010
This is version 53 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)