PTEN
entrez
5728
canonical
uniprot
P60484
canonical
ensembl
ENSG00000171862
resolver
ensembl
ENSG00000284792
resolver
ensp
ENSP00000361021
resolver
ensp
ENSP00000509861
resolver
genesymbol
PTEN
resolver
genesymbol_syn
MMAC1
resolver
genesymbol_syn
TEP1
resolver
hgnc
HGNC:9588
resolver
uniprot
B2R904
resolver
uniprot
F2YHV0
resolver
uniprot
F6KD01
resolver
uniprot
O00633
resolver
uniprot
O02679
resolver
uniprot
Q6ICT7
resolver
uniprot_entry
F6KD01_HUMAN
resolver
uniprot_entry
PTEN_HUMAN
resolver
uniprot_sec
B2R904
resolver
uniprot_sec
F2YHV0
resolver
uniprot_sec
O00633
resolver
uniprot_sec
O02679
resolver
uniprot_sec
Q6ICT7
resolver
activity_regulation
ACTIVITY REGULATION: Enzymatic activity is enhanced in the presence of phosphatidylserine. {ECO:0000269|PubMed:16824732}.
uniprot
proteins
amino_acid_sequence
MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSYLLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMYFEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEIDSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEASSSTSVTPDVSDNEPDHYRYSDTTDSDPENEPFDEDQHTQITKV
uniprot
proteins
disease_involvement
DISEASE: Cowden syndrome 1 (CWS1) [MIM:158350]: An autosomal dominant hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. {ECO:0000269|PubMed:10051160, ECO:0000269|PubMed:10234502, ECO:0000269|PubMed:10400993, ECO:0000269|PubMed:10772390, ECO:0000269|PubMed:10866302, ECO:0000269|PubMed:11230179, ECO:0000269|PubMed:11494117, ECO:0000269|PubMed:15355975, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:21659347, ECO:0000269|PubMed:24778394, ECO:0000269|PubMed:9140396, ECO:0000269|PubMed:9241266, ECO:0000269|PubMed:9259288, ECO:0000269|PubMed:9345101, ECO:0000269|PubMed:9399897, ECO:0000269|PubMed:9425889, ECO:0000269|PubMed:9467011, ECO:0000269|PubMed:9593664, ECO:0000269|PubMed:9600246, ECO:0000269|PubMed:9735393, ECO:0000269|PubMed:9797362, ECO:0000269|PubMed:9811831, ECO:0000269|PubMed:9832031, ECO:0000269|PubMed:9915974}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Lhermitte-Duclos disease (LDD) [MIM:158350]: A rare disease characterized by the occurrence of a slowly enlarging mass within the cerebellar cortex corresponding histologically to a cerebellar hamartoma. It manifests, most commonly in the third and fourth decades of life, with increased intracranial pressure, headache, nausea, cerebellar dysfunction, occlusive hydrocephalus, ataxia, visual disturbances and other cranial nerve palsies. Various associated abnormalities may be present such as megalencephaly, microgyria, hydromyelia, polydactyly, partial gigantism, macroglossia. LDD is part of the PTEN hamartoma tumor syndromes spectrum that also includes Cowden syndrome. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355]: A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. {ECO:0000269|PubMed:11801303}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. {ECO:0000269|PubMed:16506206}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Note=PTEN mutations are found in a subset of patients with Proteus syndrome, a genetically heterogeneous condition. The molecular diagnosis of PTEN mutation positive cases classifies Proteus syndrome patients as part of the PTEN hamartoma syndrome spectrum. As such, patients surviving the early years of Proteus syndrome are likely at a greater risk of developing malignancies.; DISEASE: Glioma 2 (GLM2) [MIM:613028]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269|PubMed:12085208}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Prostate cancer (PC) [MIM:176807]: A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:26504226, ECO:0000269|PubMed:9072974}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Macrocephaly/autism syndrome (MCEPHAS) [MIM:605309]: Patients have autism spectrum disorders and macrocephaly, with head circumferences ranging from +2.5 to +8 SD for age and sex (average head circumference +4.0 SD). {ECO:0000269|PubMed:15805158, ECO:0000269|PubMed:23160955, ECO:0000269|PubMed:26637798}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome, which shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome.
uniprot
proteins
ec_number
3.1.3.-
uniprot
proteins
ec_number
3.1.3.16
uniprot
proteins
ec_number
3.1.3.48
uniprot
proteins
ec_number
3.1.3.67
uniprot
proteins
function
FUNCTION: Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (PubMed:9187108, PubMed:9256433, PubMed:9616126). Also functions as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring of PtdIns(3,4,5)P3/phosphatidylinositol 3,4,5-trisphosphate, PtdIns(3,4)P2/phosphatidylinositol 3,4-diphosphate and PtdIns3P/phosphatidylinositol 3-phosphate with a preference for PtdIns(3,4,5)P3 (PubMed:16824732, PubMed:26504226, PubMed:9593664, PubMed:9811831). Furthermore, this enzyme can also act as a cytosolic inositol 3-phosphatase acting on Ins(1,3,4,5,6)P5/inositol 1,3,4,5,6 pentakisphosphate and possibly Ins(1,3,4,5)P4/1D-myo-inositol 1,3,4,5-tetrakisphosphate (PubMed:11418101, PubMed:15979280). Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (PubMed:31492966, PubMed:37279284). The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation (PubMed:11707428). In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement (PubMed:22279049). Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation (PubMed:22279049). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces PTEN phosphorylation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 and results in translocation of the PTEN-DLC1 complex to the posterior of migrating cells to promote RHOA activation (PubMed:26166433). Meanwhile, TNS3 switches binding preference from DLC1 to p85 and the TNS3-p85 complex translocates to the leading edge of migrating cells to activate RAC1 activation (PubMed:26166433). 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 (By similarity). Involved in the regulation of synaptic function in excitatory hippocampal synapses. Recruited to the postsynaptic membrane upon NMDA receptor activation, is required for the modulation of synaptic activity during plasticity. Enhancement of lipid phosphatase activity is able to drive depression of AMPA receptor-mediated synaptic responses, activity required for NMDA receptor-dependent long-term depression (LTD) (By similarity). 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 (PubMed:10468583, PubMed:18716620). {ECO:0000250|UniProtKB:O08586, ECO:0000250|UniProtKB:O54857, ECO:0000269|PubMed:10468583, ECO:0000269|PubMed:11418101, ECO:0000269|PubMed:11707428, ECO:0000269|PubMed:15979280, ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:22279049, ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26504226, ECO:0000269|PubMed:31492966, ECO:0000269|PubMed:37279284, ECO:0000269|PubMed:9187108, ECO:0000269|PubMed:9256433, ECO:0000269|PubMed:9593664, ECO:0000269|PubMed:9616126, ECO:0000269|PubMed:9811831}.; FUNCTION: [Isoform alpha]: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1. {ECO:0000269|PubMed:23744781}.
uniprot
proteins
mass_dalton
47166
uniprot
proteins
mutagenesis
MUTAGEN 1; /note="M->I: Prevents expression of isoform 1 and increased expression of isoform alpha."; /evidence="ECO:0000269|PubMed:24768297"; MUTAGEN 13; /note="K->E: Nuclear. Cytoplasmic; when associated with E-289. Shows less tumor suppressive ability; when associated with E-289."; /evidence="ECO:0000269|PubMed:18716620"; MUTAGEN 92; /note="D->A: 700-fold reduction in phosphatase activity towards PtdIns(3,4,5)P3. Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation."; /evidence="ECO:0000269|PubMed:10555148, ECO:0000269|PubMed:9616126"; MUTAGEN 93; /note="H->A: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Modest reduction in phosphatase activity towards PtdIns(3,4)P2."; /evidence="ECO:0000269|PubMed:10555148"; MUTAGEN 124; /note="C->A: Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation."; /evidence="ECO:0000269|PubMed:9616126"; MUTAGEN 125; /note="K->M: Reduced phosphatase activity towards PtdIns(3,4,5)P3, PtdIns(3,4)P2 and PtdIns(3)P."; /evidence="ECO:0000269|PubMed:10555148"; MUTAGEN 126; /note="A->P: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3 and PtdIns(3,4)P2."; /evidence="ECO:0000269|PubMed:26504226"; MUTAGEN 126; /note="A->S: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3 and PtdIns(3,4)P2."; /evidence="ECO:0000269|PubMed:26504226"; MUTAGEN 126; /note="A->V: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3 and PtdIns(3,4)P2."; /evidence="ECO:0000269|PubMed:26504226"; MUTAGEN 128; /note="K->M: 85% reduction in phosphatase activity towards PtdIns(3,4,5)P3."; /evidence="ECO:0000269|PubMed:10555148"; MUTAGEN 128; /note="K->R: Does not reduce phosphatase activity towards PtdIns(3,4,5)P3."; /evidence="ECO:0000269|PubMed:10555148"; MUTAGEN 130; /note="R->M: Does not affect the ability to inhibit AKT/PKB activation."; /evidence="ECO:0000269|PubMed:9811831"; MUTAGEN 167; /note="T->A,D: 60% reduction in phosphatase activity towards PtdIns(3,4,5)P3."; /evidence="ECO:0000269|PubMed:10555148"; MUTAGEN 171; /note="Q->A,E: 75% reduction in phosphatase activity towards PtdIns(3,4,5)P3."; /evidence="ECO:0000269|PubMed:10555148"; MUTAGEN 229; /note="S->A: No effect on interaction with DLC1 or p85."; /evidence="ECO:0000269|PubMed:26166433"; MUTAGEN 232; /note="T->A: No effect on interaction with DLC1 or p85."; /evidence="ECO:0000269|PubMed:26166433"; MUTAGEN 263..269; /note="KMLKKDK->AAGAADA: Reduces the growth suppression activity and cells show anchorage-independent growth. Reduces binding to phospholipid membranes in vitro. Phosphatase activity towards PtdIns(3,4,5)P3 is not affected."; /evidence="ECO:0000269|PubMed:10555148"; MUTAGEN 289; /note="K->E: Cytoplasmic; when associated with E-13. Shows less tumor suppressive ability; when associated with E-13."; /evidence="ECO:0000269|PubMed:18716620"; MUTAGEN 319; /note="T->A: Reduces phosphorylation of the C2 tensin-like domain and abolishes interaction with DLC1 following EGF stimulation. Abolishes phosphorylation of the C2 tensin-like domain; when associated with A-321."; /evidence="ECO:0000269|PubMed:26166433"; MUTAGEN 319; /note="T->E: Constitutive interaction with DLC1."; /evidence="ECO:0000269|PubMed:26166433"; MUTAGEN 319; /note="T->Y: Constitutive interaction with DLC1 and interaction with p85 following EGF stimulation."; /evidence="ECO:0000269|PubMed:26166433"; MUTAGEN 321; /note="T->A: Reduces phosphorylation of the C2 tensin-like domain and abolishes interaction with DLC1 following EGF stimulation. Abolishes phosphorylation of the C2 tensin-like domain; when associated with A-319."; /evidence="ECO:0000269|PubMed:26166433"; MUTAGEN 321; /note="T->E: Constitutive interaction with DLC1."; /evidence="ECO:0000269|PubMed:26166433"; MUTAGEN 327..335; /note="KANKDKANR->AAGADAANA: Reduces growth suppression activity and promotes anchorage-independent growth. Reduces binding to phospholipid membranes in vitro; phosphatase activity towards PtdIns(3,4,5)P3 is not affected."; /evidence="ECO:0000269|PubMed:10555148"; MUTAGEN 336; /note="Y->F: Significantly lower phosphatase activity, reduced protein stability and decreased growth-inhibitory effect."; /evidence="ECO:0000269|PubMed:19345329"; MUTAGEN 366; /note="T->A: Decreased stability."; /evidence="ECO:0000269|PubMed:20940307"; MUTAGEN 370; /note="S->A: Decreased stability."; /evidence="ECO:0000269|PubMed:20940307"; MUTAGEN 401; /note="T->A: Loss of DLG1-binding. No effect on MAGI2- and MAST2-binding."; MUTAGEN 402; /note="K->A: No effect on MAGI2-, MAST2- and DLG1-binding."; MUTAGEN 402; /note="K->W: Loss of DLG1-, MAGI2-, MAGI3- and MAST2-binding. Decrease of protein stability."; MUTAGEN 403; /note="V->A: Loss of DLG1-, MAGI2-, MAGI3-, MAST1-, MAST2- and MAST3-binding."; /evidence="ECO:0000269|PubMed:15951562
uniprot
proteins
post_translational_modification
PTM: Constitutively phosphorylated by CK2 under normal conditions. Phosphorylated in vitro by MAST1, MAST2, MAST3 and STK11. 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. Phosphorylated on Thr-319 and Thr-321 in the C2-type tensin domain following EGF stimulation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 (PubMed:26166433). {ECO:0000269|PubMed:10646847, ECO:0000269|PubMed:11035045, ECO:0000269|PubMed:11707428, ECO:0000269|PubMed:12297295, ECO:0000269|PubMed:15951562, ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:19345329, ECO:0000269|PubMed:20940307, ECO:0000269|PubMed:26166433}.; PTM: 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. Ubiquitinated by XIAP/BIRC4. {ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:19473982}.; PTM: Ubiquitinated by the DCX(DCAF13) E3 ubiquitin ligase complex, leading to its degradation. {ECO:0000269|PubMed:31492966}.; PTM: ISGylated. ISGylation promotes PTEN degradation. {ECO:0000269|PubMed:37279284}.
uniprot
proteins
protein_family
PTEN phosphatase protein family
uniprot
proteins
pubmed
10051160
uniprot
proteins
pubmed
10234502
uniprot
proteins
pubmed
10400993
uniprot
proteins
pubmed
10468583
uniprot
proteins
pubmed
10555148
uniprot
proteins
pubmed
10646847
uniprot
proteins
pubmed
10748157
uniprot
proteins
pubmed
10760291
uniprot
proteins
pubmed
10772390
uniprot
proteins
pubmed
10807691
uniprot
proteins
pubmed
10817502
uniprot
proteins
pubmed
10866302
uniprot
proteins
pubmed
10978354
uniprot
proteins
pubmed
11035045
uniprot
proteins
pubmed
11230179
uniprot
proteins
pubmed
11418101
uniprot
proteins
pubmed
11494117
uniprot
proteins
pubmed
11707428
uniprot
proteins
pubmed
11748304
uniprot
proteins
pubmed
11801303
uniprot
proteins
pubmed
12085208
uniprot
proteins
pubmed
12297295
uniprot
proteins
pubmed
12471211
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15355975
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15805158
uniprot
proteins
pubmed
15951562
uniprot
proteins
pubmed
15979280
uniprot
proteins
pubmed
15987703
uniprot
proteins
pubmed
16506206
uniprot
proteins
pubmed
16752378
uniprot
proteins
pubmed
16824732
uniprot
proteins
pubmed
17218260
uniprot
proteins
pubmed
17436248
uniprot
proteins
pubmed
18716620
uniprot
proteins
pubmed
19345329
uniprot
proteins
pubmed
19473982
uniprot
proteins
pubmed
20534535
uniprot
proteins
pubmed
20940307
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21659347
uniprot
proteins
pubmed
22279049
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23160955
uniprot
proteins
pubmed
23744781
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24768297
uniprot
proteins
pubmed
24778394
uniprot
proteins
pubmed
25007873
uniprot
proteins
pubmed
25801959
uniprot
proteins
pubmed
26166433
uniprot
proteins
pubmed
26504226
uniprot
proteins
pubmed
26637798
uniprot
proteins
pubmed
31492966
uniprot
proteins
pubmed
37279284
uniprot
proteins
pubmed
39316756
uniprot
proteins
pubmed
9072974
uniprot
proteins
pubmed
9090379
uniprot
proteins
pubmed
9140396
uniprot
proteins
pubmed
9187108
uniprot
proteins
pubmed
9241266
uniprot
proteins
pubmed
9256433
uniprot
proteins
pubmed
9259288
uniprot
proteins
pubmed
9331071
uniprot
proteins
pubmed
9345101
uniprot
proteins
pubmed
9399897
uniprot
proteins
pubmed
9425889
uniprot
proteins
pubmed
9467011
uniprot
proteins
pubmed
9593664
uniprot
proteins
pubmed
9600246
uniprot
proteins
pubmed
9616126
uniprot
proteins
pubmed
9635567
uniprot
proteins
pubmed
9735393
uniprot
proteins
pubmed
9797362
uniprot
proteins
pubmed
9811831
uniprot
proteins
pubmed
9832031
uniprot
proteins
pubmed
9915974
uniprot
proteins
sequence_length
403
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:19473982, ECO:0000269|PubMed:25801959, ECO:0000269|PubMed:9187108}. Nucleus {ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:19473982, ECO:0000269|PubMed:25801959}. Nucleus, PML body {ECO:0000269|PubMed:18716620}. Cell projection, dendritic spine {ECO:0000250|UniProtKB:O54857}. Postsynaptic density {ECO:0000250|UniProtKB:O54857}. Note=Monoubiquitinated form is nuclear. Nonubiquitinated form is cytoplasmic. Colocalized with PML and USP7 in PML nuclear bodies (PubMed:18716620). XIAP/BIRC4 promotes its nuclear localization (PubMed:19473982). Associates with the postsynaptic density in response to NMDAR activation (By similarity). {ECO:0000250|UniProtKB:O54857, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:19473982}.; SUBCELLULAR LOCATION: [Isoform alpha]: Secreted {ECO:0000269|PubMed:23744781, ECO:0000269|PubMed:24768297}. Note=May be secreted via a classical signal peptide and reenter into cells with the help of a poly-Arg motif. {ECO:0000269|PubMed:23744781, ECO:0000269|PubMed:24768297}.
uniprot
proteins