Protein:PTEN |
Protein Summary |
 Gene summary |
| Gene name: PTEN | ASpdb.0 ID: 5728 | Gene | Gene symbol | PTEN | Gene ID | 5728 |
| Gene name | phosphatase and tensin homolog |
| Synonyms | 10q23del|BZS|CWS1|DEC|GLM2|MHAM|MMAC1|PTEN1|PTENbeta|TEP1 |
| Cytomap | 10q23.31 |
| Type of gene | protein-coding |
| Description | phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENMMAC1 phosphatase and tensin homolog deleted on chromosome 10PTEN variant PTEN-K267Rfs*9PTEN variant PTEN-L247*PTEN variant PTEN-R234Afs*11PTENepsilon |
| Modification date | 20240416 |
| UniProtAcc | P60484 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | PTEN | GO:0001933 | negative regulation of protein phosphorylation | 20123964 |
| Gene | PTEN | GO:0004438 | phosphatidylinositol-3-phosphate phosphatase activity | 9811831 |
| Gene | PTEN | GO:0004721 | phosphoprotein phosphatase activity | 21241890 |
| Gene | PTEN | GO:0004722 | protein serine/threonine phosphatase activity | 9256433 |
| Gene | PTEN | GO:0004725 | protein tyrosine phosphatase activity | 9256433 |
| Gene | PTEN | GO:0005634 | nucleus | 17218261|21241890|24862762 |
| Gene | PTEN | GO:0005654 | nucleoplasm | - |
| Gene | PTEN | GO:0005737 | cytoplasm | 9187108|10760291|10940933|21241890|24862762 |
| Gene | PTEN | GO:0005829 | cytosol | - |
| Gene | PTEN | GO:0005886 | plasma membrane | 10760291 |
| Gene | PTEN | GO:0006470 | protein dephosphorylation | 9256433 |
| Gene | PTEN | GO:0007056 | spindle assembly involved in female meiosis | 31492966 |
| Gene | PTEN | GO:0008285 | negative regulation of cell population proliferation | 19057511 |
| Gene | PTEN | GO:0009898 | cytoplasmic side of plasma membrane | 10940933 |
| Gene | PTEN | GO:0016314 | phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity | 9593664|9811831 |
| Gene | PTEN | GO:0030351 | inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity | 11418101 |
| Gene | PTEN | GO:0042995 | cell projection | 10760291|25007873 |
| Gene | PTEN | GO:0045736 | negative regulation of cyclin-dependent protein serine/threonine kinase activity | 21241890 |
| Gene | PTEN | GO:0046856 | phosphatidylinositol dephosphorylation | 9811831 |
| Gene | PTEN | GO:0050821 | protein stabilization | 20123964 |
| Gene | PTEN | GO:0051717 | inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity | 9593664 |
| Gene | PTEN | GO:0051800 | phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity | 9811831 |
| Gene | PTEN | GO:0051898 | negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 31492966 |
| Gene | PTEN | GO:0052866 | phosphatidylinositol phosphate phosphatase activity | 9811831 |
| Gene | PTEN | GO:0060070 | canonical Wnt signaling pathway | 20123964 |
| Gene | PTEN | GO:1902807 | negative regulation of cell cycle G1/S phase transition | 10918569 |
| Gene | PTEN | GO:1904668 | positive regulation of ubiquitin protein ligase activity | 21241890 |
| Gene | PTEN | GO:2000060 | positive regulation of ubiquitin-dependent protein catabolic process | 21241890 |
| Gene | PTEN | GO:2000134 | negative regulation of G1/S transition of mitotic cell cycle | 21241890 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P60484-1 | P60484-1_1d5r_A.pdb | 1D5R | X-ray | 2.1 | A | 14 | 351 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P60484 | PTEN | P60484-1 | P60484-2 | 403 | 576 | 1 | 1 | Substitution | M | MERGGEAAAAAAAAAAAPGRGSESPVTISRAGNAGELVSPLLLPPTRRRRRRHIQGPGPVLNLPSAAAAPPVARAPEAAGGGSRSEDYSSSPHSAAAAARPLAAEEKQAQSLQPSSSRRSSHYPAAVQSQAAAERGASATAKSRAISILQKKPRHQQLLPSLSSFFFSHRLPDM | 1 | 174 |
| P60484 | PTEN | P60484-1 | P60484-3 | 403 | 175 | 55 | 70 | Substitution | RFLDSKHKNHYKIYNL | S | 55 | 55 |
| P60484 | PTEN | P60484-1 | P60484-3 | 403 | 175 | 165 | 190 | Substitution | GVTIPSQRRYVYYYSYLLKNHLDYRP | ADPTGGIPDKGIIVIGDGSSMDVIAP | 150 | 175 |
| P60484 | PTEN | P60484-1 | P60484-3 | 403 | 175 | 191 | 403 | Deletion | none | none | 175 | 175 |
| Multiple sequence alignment of our canonical and alternatively spliced PTEN |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of PTEN |
| UniProt-id | ENSG | ENST | ENSP |
| P60484-1 | ENSG00000171862.15 | ENST00000371953.8 | ENSP00000361021.3 |
| P60484-1 | ENSG00000284792.2 | ENST00000644628.2 | ENSP00000494918.2 |
| P60484-1 | ENSG00000171862.15 | ENST00000688308.1 | ENSP00000508752.1 |
| P60484-1 | ENSG00000284792.2 | ENST00000710385.1 | ENSP00000518242.1 |
| P60484-2 | ENSG00000284792.2 | ENST00000710387.1 | ENSP00000518244.1 |
| UniProt-id | NM ID | NP ID |
| P60484-1 | NM_000314.6 | NP_000305.3 |
| Amino acid sequences of our canonical and alternatively spliced PTEN |
| accession_id | Protein sequence |
| P60484-1 | MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPF EDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSY LLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMYFEFPQPLPVCGDIKVEFFHKQNKMLKKDKM FHFWVNTFFIPGPEETSEKVENGSLCDQEIDSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEAS |
| P60484-2 | MERGGEAAAAAAAAAAAPGRGSESPVTISRAGNAGELVSPLLLPPTRRRRRRHIQGPGPVLNLPSAAAAPPVARAPEAAGGGSRSEDYSS SPHSAAAAARPLAAEEKQAQSLQPSSSRRSSHYPAAVQSQAAAERGASATAKSRAISILQKKPRHQQLLPSLSSFFFSHRLPDMTAIIKE IVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQ LELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSYLLKNHLD YRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMYFEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNT FFIPGPEETSEKVENGSLCDQEIDSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEASSSTSVTP |
| P60484-3 | MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVSCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFC |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| PTEN (go to UniProt):P60484 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P60484 | Domain | 14 | 185 | Note=Phosphatase tensin-type;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00590 | Type=Substitution;Start=55;End=70 |
| P60484 | Domain | 14 | 185 | Note=Phosphatase tensin-type;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00590 | Type=Substitution;Start=165;End=190 |
| P60484 | Domain | 190 | 350 | Note=C2 tensin-type;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00589 | Type=Substitution;Start=165;End=190 |
| P60484 | Domain | 190 | 350 | Note=C2 tensin-type;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00589 | Type=Deletion;Start=191;End=403 |
| P60484 | Region | 338 | 348 | Note=Required for interaction with NOP53;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:15355975;Dbxref=PMID:15355975 | Type=Deletion;Start=191;End=403 |
| P60484 | Region | 352 | 403 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=191;End=403 |
| P60484 | Motif | 401 | 403 | Note=PDZ domain-binding;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:O08586 | Type=Deletion;Start=191;End=403 |
| P60484 | Compositional bias | 353 | 370 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=191;End=403 |
| P60484 | Compositional bias | 371 | 385 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=191;End=403 |
Gene Isoform Structures and Expression Levels for PTEN |
| Gene structures of our canonical and alternative spliced genes of PTEN * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P60484-1 |
| 3D view using mol* of P60484-2 |
| 3D view using mol* of P60484-3 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P60484-1 |
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| pLDDT distribution across the protein length of P60484-2 |
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| pLDDT distribution across the protein length of P60484-3 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P60484-1 |
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| Ramachandran plot of P60484-2 |
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| Ramachandran plot of P60484-3 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P60484-1 | 1.029 | 178 | 1.057 | 665.763 | 0.62 | 0.721 | 0.924 | 0.547 | 0.969 | 0.565 | 0.749 | 72,73,74,89,90,91,92,93,94,95,96,97,125,167,168,20 6,216,217,218,220,221,254,255,256,258,269,270,272, 274,326,327,328,330,331,332,333,335,336,337,379,38 4,385,387,388 |
| P60484-2 | 1.026 | 447 | 1.022 | 1587.404 | 0.567 | 0.737 | 0.937 | 0.486 | 1.104 | 0.44 | 0.616 | 179,182,183,184,185,186,188,197,209,210,219,220,22 1,245,246,247,262,263,264,265,266,267,268,269,270, 273,297,298,299,301,302,303,322,333,335,337,338,33 9,340,341,342,344,345,346,349,350,379,389,390,391, 393,394,425,427,428,429,431,442,445,447,452,472,47 3,475,476,478,491,492,494,496,497,499,500,501,502, 503,504,505,506,509,510,552,554,555,556,557,558,55 9,560,561,562,563 |
| P60484-3 | 0.961 | 56 | 0.964 | 178.017 | 0.462 | 0.821 | 0.99 | 1.453 | 0.712 | 2.04 | 0.904 | 35,37,38,50,53,65,66,70,72,106,108,163,165,166,167 ,169,170,173 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P60484-1_P60484-1_1d5r_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P60484-1_1d5r_A_P60484-2.pdb |
| 3D view using mol* of P60484-1_1d5r_A_P60484-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P60484-1_P60484-2.pdb |
| 3D view using mol* of P60484-1_P60484-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P60484-1_vs_P60484-2.png |
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| ./stats/secondary_structure/figure/P60484-1_vs_P60484-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P60484-1_vs_P60484-2.png |
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| ./stats/relative_asa/P60484-1_vs_P60484-3.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P60484 | Region | 338 | 348 | Note=Required for interaction with NOP53;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:15355975;Dbxref=PMID:15355975 | Type=Deletion;Start=191;End=403 |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to PTEN |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P60484 | PTEN | DB04327 | Phosphatidylethanolamine | experimental | substrate |
Related Diseases to PTEN |
| Previous studies relating to the alternative splicing of PTEN and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| PTEN | 16436456 | Differential expression of novel naturally occurring splice variants of PTEN and their functional consequences in Cowden syndrome and sporadic breast cancer. | PTEN, a dual-phosphatase tumor suppressor, is inactivated in Cowden syndrome (CS), characterized by high risk of breast and thyroid cancer, and in variety of sporadic cancers. Despite the importance of alternative splicing, very limited information on its role in PTEN and associated cancers is available. We identified eight novel PTEN splice variants (SVs) that retained intron 3 regions (3a, 3b, 3c); intron 5 regions (5a, 5b, 5c); excluded part of exon 5 (DelE5) or all of exon 6 (DelE6), respectively. Analysis of SVs in 12 sporadic breast cancers revealed full-length (FL)-PTEN transcript reduction in 10; SVs 3b, 3c and 5c not expressed in 7, 6 and 4, respectively, and under-expressed in the rest. In contrast, SV-5b was over-expressed in breast cancers. PTEN SV analysis in 16 CS/CS-like patients and eight controls revealed that SV-5a is under-expressed and SV-3a over-expressed in the germline of CS/CS-like individuals when compared with controls. Although SV-5a expression decreased P-Akt level and cyclin D1 promoter activity, SVs 5b and 5c increased cyclin D1 promoter activity. Thus, SV-5a behaving like FL-PTEN corroborates our observation that SV-5a is under-expressed in CS when compared with controls. Similarly, SV-5b functionally counters PTEN's action and is over-expressed in sporadic breast cancers. Furthermore, we demonstrate that expression of these SVs is under the regulation of p53. Our observations suggest that differential expression of PTEN and its SVs could play a role in the pathogenesis of sporadic breast cancers and CS, and may lend a novel way of making a rapid molecular diagnosis of CS without mutation analysis. | D001943 | Breast Neoplasms |
| PTEN | 16436456 | Differential expression of novel naturally occurring splice variants of PTEN and their functional consequences in Cowden syndrome and sporadic breast cancer. | PTEN, a dual-phosphatase tumor suppressor, is inactivated in Cowden syndrome (CS), characterized by high risk of breast and thyroid cancer, and in variety of sporadic cancers. Despite the importance of alternative splicing, very limited information on its role in PTEN and associated cancers is available. We identified eight novel PTEN splice variants (SVs) that retained intron 3 regions (3a, 3b, 3c); intron 5 regions (5a, 5b, 5c); excluded part of exon 5 (DelE5) or all of exon 6 (DelE6), respectively. Analysis of SVs in 12 sporadic breast cancers revealed full-length (FL)-PTEN transcript reduction in 10; SVs 3b, 3c and 5c not expressed in 7, 6 and 4, respectively, and under-expressed in the rest. In contrast, SV-5b was over-expressed in breast cancers. PTEN SV analysis in 16 CS/CS-like patients and eight controls revealed that SV-5a is under-expressed and SV-3a over-expressed in the germline of CS/CS-like individuals when compared with controls. Although SV-5a expression decreased P-Akt level and cyclin D1 promoter activity, SVs 5b and 5c increased cyclin D1 promoter activity. Thus, SV-5a behaving like FL-PTEN corroborates our observation that SV-5a is under-expressed in CS when compared with controls. Similarly, SV-5b functionally counters PTEN's action and is over-expressed in sporadic breast cancers. Furthermore, we demonstrate that expression of these SVs is under the regulation of p53. Our observations suggest that differential expression of PTEN and its SVs could play a role in the pathogenesis of sporadic breast cancers and CS, and may lend a novel way of making a rapid molecular diagnosis of CS without mutation analysis. | D006223 | Hamartoma Syndrome, Multiple |
| PTEN | 16436456 | Differential expression of novel naturally occurring splice variants of PTEN and their functional consequences in Cowden syndrome and sporadic breast cancer. | PTEN, a dual-phosphatase tumor suppressor, is inactivated in Cowden syndrome (CS), characterized by high risk of breast and thyroid cancer, and in variety of sporadic cancers. Despite the importance of alternative splicing, very limited information on its role in PTEN and associated cancers is available. We identified eight novel PTEN splice variants (SVs) that retained intron 3 regions (3a, 3b, 3c); intron 5 regions (5a, 5b, 5c); excluded part of exon 5 (DelE5) or all of exon 6 (DelE6), respectively. Analysis of SVs in 12 sporadic breast cancers revealed full-length (FL)-PTEN transcript reduction in 10; SVs 3b, 3c and 5c not expressed in 7, 6 and 4, respectively, and under-expressed in the rest. In contrast, SV-5b was over-expressed in breast cancers. PTEN SV analysis in 16 CS/CS-like patients and eight controls revealed that SV-5a is under-expressed and SV-3a over-expressed in the germline of CS/CS-like individuals when compared with controls. Although SV-5a expression decreased P-Akt level and cyclin D1 promoter activity, SVs 5b and 5c increased cyclin D1 promoter activity. Thus, SV-5a behaving like FL-PTEN corroborates our observation that SV-5a is under-expressed in CS when compared with controls. Similarly, SV-5b functionally counters PTEN's action and is over-expressed in sporadic breast cancers. Furthermore, we demonstrate that expression of these SVs is under the regulation of p53. Our observations suggest that differential expression of PTEN and its SVs could play a role in the pathogenesis of sporadic breast cancers and CS, and may lend a novel way of making a rapid molecular diagnosis of CS without mutation analysis. | D013577 | Syndrome |
Clinically important variants in PTEN |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
| P60484 | P60484-1 | PTEN | Deletion | p.Asp268Thrfs | Likely pathogenic |
| P60484 | P60484-1 | PTEN | Deletion | p.Asp268Thrfs | Likely pathogenic |
| P60484 | P60484-1 | PTEN | Insertion | p.Val290Lysfs | Likely pathogenic |
| P60484 | P60484-1 | PTEN | Insertion | p.Val290Lysfs | Likely pathogenic |
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