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Details on Person UniProt:P60484 PTEN
| Class:Id | ReferenceGeneProduct:62405 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 6 2015;chain:2-403 added on Fri February 6 2015;initiator methionine:1 for 62405 removed on Fri Nov 03 2023;initiator methionine: for 62405 added on Fri Nov 03 2023;initiator methionine: for 62405 removed on Fri Aug 15 2025;initiator methionine:1 for 62405 added on Fri Aug 15 2025 |
| _displayName | UniProt:P60484 PTEN |
| _timestamp | 2025-08-15 21:10:16 |
| chain | initiator methionine:1 chain:2-403 |
| checksum | 75F97C3DD6802BA9 |
| comment | 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).FUNCTION 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.CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + phosphateCATALYTIC ACTIVITY O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphateCATALYTIC ACTIVITY O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphateCATALYTIC ACTIVITY O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphateCATALYTIC ACTIVITY 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + phosphateCATALYTIC ACTIVITY 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + phosphateCATALYTIC ACTIVITY 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + H2O = 1D-myo-inositol 1,4,5,6-tetrakisphosphate + phosphateCATALYTIC ACTIVITY 1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + phosphateCOFACTOR Enzymatic activity is enhanced in the presence of phosphatidylserine.BIOPHYSICOCHEMICAL PROPERTIES Monomer. The unphosphorylated form interacts with the second PDZ domain of MAGI2 and with DLG1 and MAST2 in vitro (PubMed:10646847, PubMed:10760291, PubMed:11707428). Interacts with MAGI2, MAGI3, MAST1 and MAST3, but neither with MAST4 nor with DLG5; interaction with MAGI2 increases protein stability (PubMed:10748157, PubMed:15951562). Interacts with NEDD4 (PubMed:17218260). Interacts with NDFIP1 and NDFIP2; in the presence of NEDD4 or ITCH, this interaction promotes PTEN ubiquitination (PubMed:20534535, PubMed:25801959). Interacts (via C2 domain) with FRK (PubMed:19345329). Interacts with USP7; the interaction is direct (PubMed:18716620). Interacts with ROCK1 (By similarity). Interacts with XIAP/BIRC4 (PubMed:19473982). Interacts with STK11; the interaction phosphorylates PTEN (PubMed:15987703). Interacts with PPP1R16B (PubMed:25007873). Interacts with NOP53; regulates PTEN phosphorylation and increases its stability (PubMed:15355975). Interacts (via PDZ domain-binding motif) with DLG4; the interaction is induced by NMDA and is required for PTEN location at postsynaptic density (By similarity). Interacts with the regulatory p85 subunit of the PI3K kinase complex and with Rho GTPase-activating protein DLC1; in resting cells, interacts (via C2 tensin-type domain) with p85 but, following growth factor stimulation, PTEN is phosphorylated which leads to weakened interaction with p85 and enhanced interaction (via C2 tensin-type domain) with DLC1 while p85 interaction with TNS3 increases (PubMed:26166433).INTERACTION 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). Associares with the postsynaptic density in response to NMDAR activation (By similarity).SUBCELLULAR LOCATION May be secreted via a classical signal peptide and reenter into cells with the help of a poly-Arg motif.ALTERNATIVE PRODUCTS Expressed at a relatively high level in all adult tissues, including heart, brain, placenta, lung, liver, muscle, kidney and pancreas.INDUCTION Down-regulated by TGFB1.DOMAIN The C2 domain binds phospholipid membranes in vitro in a Ca(2+)-independent manner; this binding is important for its tumor suppressor function.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).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.PTM Ubiquitinated by the DCX(DCAF13) E3 ubiquitin ligase complex, leading to its degradation.PTM ISGylated. ISGylation promotes PTEN degradation.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE 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 Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE 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.MISCELLANEOUS Produced by alternative initiation at an upstream CTG start codon. May contain a signal peptide at positions 1-21.SIMILARITY Belongs to the PTEN phosphatase protein family. |
| description | recommendedName: fullName evidence="81 83"Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN ecNumber evidence="60"3.1.3.16 ecNumber evidence="58 60"3.1.3.48 ecNumber evidence="34 73"3.1.3.67 alternativeName: fullName evidence="79 82"Inositol polyphosphate 3-phosphatase ecNumber evidence="79 82"3.1.3.- alternativeName: Mutated in multiple advanced cancers 1 alternativeName: Phosphatase and tensin homolog |
| geneName | PTEN MMAC1 TEP1 |
| identifier | P60484 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative initiation Alternative splicing Apoptosis Autism spectrum disorder Cell projection Cytoplasm Disease variant Hydrolase Isopeptide bond Lipid metabolism Lipid-binding Neurogenesis Nucleus Phosphoprotein Protein phosphatase Proteomics identification Reference proteome Secreted Synapse Tumor suppressor Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | PTEN |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:5632940] ENSEMBL:ENSG00000171862 PTEN [Homo sapiens] |
| secondaryIdentifier | PTEN_HUMAN B2R904 F2YHV0 O00633 O02679 Q6ICT7 |
| sequenceLength | 403 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8976188] UniProt:P60484-1 PTEN [Homo sapiens] [ReferenceIsoform:8976189] UniProt:P60484-2 PTEN [Homo sapiens] [ReferenceIsoform:8976190] UniProt:P60484-3 PTEN [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:199420] PTEN [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2317339] PTEN R130G [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2317379] PTEN C124S [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2317416] PTEN R130Q [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2317430] PTEN R130L [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2317432] PTEN R130P [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2317439] PTEN C124R [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2317461] PTEN C124F [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2317464] PTEN C124Y [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2317473] PTEN R173H [cytosol] [Homo sapiens] |
| (referenceSequence) | [ReplacedResidue:2317336] L-arginine 130 replaced with glycine [ReplacedResidue:2317382] L-cysteine 124 replaced with L-serine [ReplacedResidue:2317414] L-arginine 130 replaced with L-glutamine [ReplacedResidue:2317428] L-arginine 130 replaced with L-leucine [ReplacedResidue:2317436] L-arginine 130 replaced with L-proline [ReplacedResidue:2317445] L-cysteine 124 replaced with L-arginine [ReplacedResidue:2317459] L-cysteine 124 replaced with L-phenylalanine [ReplacedResidue:2317468] L-cysteine 124 replaced with L-tyrosine [ReplacedResidue:2317470] L-arginine 173 replaced with L-histidine [ReplacedResidue:2317477] L-arginine 173 replaced with L-proline |
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No pathways have been reviewed or authored by UniProt:P60484 PTEN (62405)
