| UniProt ID | PTEN_HUMAN | |
|---|---|---|
| UniProt AC | P60484 | |
| Protein Name | Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN | |
| Gene Name | PTEN | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 403 | |
| Subcellular Localization |
Cytoplasm . Nucleus . Nucleus, PML body . 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). |
|
| Protein Description | 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. [PubMed: 26504226 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. 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. 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. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement.; 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.] | |
| Protein Sequence | MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSYLLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMYFEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEIDSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEASSSTSVTPDVSDNEPDHYRYSDTTDSDPENEPFDEDQHTQITKV | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 2 | Phosphorylation | ------MTAIIKEIV ------CCHHHHHHH | 26.94 | 27486199 | |
| 2 | Acetylation | ------MTAIIKEIV ------CCHHHHHHH | 26.94 | 22814378 | |
| 6 | Acetylation | --MTAIIKEIVSRNK --CCHHHHHHHHHCC | 34.96 | 19608861 | |
| 6 | Ubiquitination | --MTAIIKEIVSRNK --CCHHHHHHHHHCC | 34.96 | 19608861 | |
| 13 | Ubiquitination | KEIVSRNKRRYQEDG HHHHHHCCHHHHCCC | 36.82 | 18716620 | |
| 24 (in isoform 2) | Phosphorylation | - | 38.52 | 28674419 | |
| 27 | Phosphorylation | GFDLDLTYIYPNIIA CCCCCCEEECCCCCC | 13.02 | - | |
| 35 | Sulfoxidation | IYPNIIAMGFPAERL ECCCCCCCCCCHHHC | 3.91 | 29298524 | |
| 39 (in isoform 2) | Phosphorylation | - | 16.57 | 29954749 | |
| 46 | Phosphorylation | AERLEGVYRNNIDDV HHHCCCHHHCCHHHH | 20.62 | - | |
| 66 | Ubiquitination | SKHKNHYKIYNLCAE HCCCCHHHHHHHHHH | 31.03 | - | |
| 68 | Phosphorylation | HKNHYKIYNLCAERH CCCHHHHHHHHHHHC | 9.64 | 19345329 | |
| 71 | Glutathionylation | HYKIYNLCAERHYDT HHHHHHHHHHHCCCC | 3.09 | 15967877 | |
| 80 | Ubiquitination | ERHYDTAKFNCRVAQ HHCCCCCCCCCEEEC | 38.92 | - | |
| 85 (in isoform 2) | Phosphorylation | - | 4.19 | 29978859 | |
| 88 (in isoform 2) | Phosphorylation | - | 10.51 | 29978859 | |
| 89 (in isoform 2) | Phosphorylation | - | 17.67 | 29978859 | |
| 90 (in isoform 2) | Phosphorylation | - | 17.12 | 29978859 | |
| 91 (in isoform 2) | Phosphorylation | - | 54.58 | 29978859 | |
| 113 | Phosphorylation | EDLDQWLSEDDNHVA HCHHHHHCCCCCCEE | 35.70 | - | |
| 124 | Glutathionylation | NHVAAIHCKAGKGRT CCEEEEEEECCCCHH | 2.36 | 15967877 | |
| 125 | Acetylation | HVAAIHCKAGKGRTG CEEEEEEECCCCHHH | 46.11 | 16829519 | |
| 128 | Acetylation | AIHCKAGKGRTGVMI EEEEECCCCHHHHHH | 50.51 | 16829519 | |
| 134 | Sulfoxidation | GKGRTGVMICAYLLH CCCHHHHHHHHHHHH | 1.89 | 29298524 | |
| 138 | Phosphorylation | TGVMICAYLLHRGKF HHHHHHHHHHHCCCC | 12.84 | 21532586 | |
| 155 | Phosphorylation | AQEALDFYGEVRTRD HHHHHHHHHHEECCC | 16.43 | 21532586 | |
| 161 (in isoform 2) | Phosphorylation | - | 43.09 | 29954749 | |
| 163 | Acetylation | GEVRTRDKKGVTIPS HHEECCCCCCCCCCC | 48.40 | 7666197 | |
| 163 (in isoform 2) | Phosphorylation | - | 48.40 | 29954749 | |
| 164 | Acetylation | EVRTRDKKGVTIPSQ HEECCCCCCCCCCCC | 64.00 | 7666207 | |
| 170 | Phosphorylation | KKGVTIPSQRRYVYY CCCCCCCCCCHHHHH | 32.25 | 24719451 | |
| 174 | Phosphorylation | TIPSQRRYVYYYSYL CCCCCCHHHHHHHHH | 8.59 | 22817900 | |
| 175 (in isoform 2) | Phosphorylation | - | 2.05 | 29954749 | |
| 176 | Phosphorylation | PSQRRYVYYYSYLLK CCCCHHHHHHHHHHH | 6.43 | 22817900 | |
| 177 | Phosphorylation | SQRRYVYYYSYLLKN CCCHHHHHHHHHHHC | 3.95 | 22817900 | |
| 178 | Phosphorylation | QRRYVYYYSYLLKNH CCHHHHHHHHHHHCC | 3.52 | 22817900 | |
| 179 | Phosphorylation | RRYVYYYSYLLKNHL CHHHHHHHHHHHCCC | 7.99 | 24043423 | |
| 180 | Phosphorylation | RYVYYYSYLLKNHLD HHHHHHHHHHHCCCC | 10.42 | 24043423 | |
| 198 | Sulfoxidation | VALLFHKMMFETIPM HHHHHHHHHHHCCCC | 2.53 | 29298524 | |
| 199 | Sulfoxidation | ALLFHKMMFETIPMF HHHHHHHHHHCCCCC | 3.07 | 29298524 | |
| 205 | Sulfoxidation | MMFETIPMFSGGTCN HHHHCCCCCCCCCCC | 3.54 | 29298524 | |
| 223 | Ubiquitination | VVCQLKVKIYSSNSG EEEEEEEEEECCCCC | 34.05 | - | |
| 227 | O-linked_Glycosylation | LKVKIYSSNSGPTRR EEEEEECCCCCCCCC | 20.31 | 30379171 | |
| 227 | Phosphorylation | LKVKIYSSNSGPTRR EEEEEECCCCCCCCC | 20.31 | - | |
| 229 | Phosphorylation | VKIYSSNSGPTRRED EEEECCCCCCCCCCC | 48.36 | 22817900 | |
| 232 | Phosphorylation | YSSNSGPTRREDKFM ECCCCCCCCCCCEEE | 45.97 | 22817900 | |
| 239 | Sulfoxidation | TRREDKFMYFEFPQP CCCCCEEEEEECCCC | 4.64 | 29298524 | |
| 240 | Phosphorylation | RREDKFMYFEFPQPL CCCCEEEEEECCCCC | 11.77 | 19345329 | |
| 254 | Sumoylation | LPVCGDIKVEFFHKQ CCCCCCCEEEEEHHH | 40.21 | - | |
| 254 | Sumoylation | LPVCGDIKVEFFHKQ CCCCCCCEEEEEHHH | 40.21 | - | |
| 266 | Sumoylation | HKQNKMLKKDKMFHF HHHCCCCCCCCEEEE | 56.26 | - | |
| 266 | Sumoylation | HKQNKMLKKDKMFHF HHHCCCCCCCCEEEE | 56.26 | - | |
| 270 | Sulfoxidation | KMLKKDKMFHFWVNT CCCCCCCEEEEEEEE | 4.53 | 29298524 | |
| 289 | Sumoylation | GPEETSEKVENGSLC CCHHHCCCCCCCCCC | 55.40 | - | |
| 289 | Sumoylation | GPEETSEKVENGSLC CCHHHCCCCCCCCCC | 55.40 | - | |
| 289 | Ubiquitination | GPEETSEKVENGSLC CCHHHCCCCCCCCCC | 55.40 | 18716620 | |
| 294 | Phosphorylation | SEKVENGSLCDQEID CCCCCCCCCCHHHHH | 37.09 | 25159151 | |
| 302 | Phosphorylation | LCDQEIDSICSIERA CCHHHHHCCEEEEEC | 31.02 | 25159151 | |
| 305 | Phosphorylation | QEIDSICSIERADND HHHHCCEEEEECCCC | 26.30 | 25627689 | |
| 315 | Phosphorylation | RADNDKEYLVLTLTK ECCCCCEEEEEEEEH | 14.09 | 19345329 | |
| 319 | Phosphorylation | DKEYLVLTLTKNDLD CCEEEEEEEEHHHHH | 25.54 | - | |
| 321 | Phosphorylation | EYLVLTLTKNDLDKA EEEEEEEEHHHHHHH | 23.67 | - | |
| 332 | Acetylation | LDKANKDKANRYFSP HHHHCHHHCCCCCCC | 49.52 | 7266279 | |
| 336 | Phosphorylation | NKDKANRYFSPNFKV CHHHCCCCCCCCEEE | 14.28 | 19345329 | |
| 338 | Phosphorylation | DKANRYFSPNFKVKL HHCCCCCCCCEEEEE | 15.25 | 27282143 | |
| 350 | Phosphorylation | VKLYFTKTVEEPSNP EEEEEEEECCCCCCC | 30.05 | 27732954 | |
| 355 | Phosphorylation | TKTVEEPSNPEASSS EEECCCCCCCCCCCC | 69.19 | 27732954 | |
| 360 | Phosphorylation | EPSNPEASSSTSVTP CCCCCCCCCCCCCCC | 24.14 | 27732954 | |
| 361 | Phosphorylation | PSNPEASSSTSVTPD CCCCCCCCCCCCCCC | 44.69 | 28857561 | |
| 362 | Phosphorylation | SNPEASSSTSVTPDV CCCCCCCCCCCCCCC | 23.39 | 16107342 | |
| 363 | Phosphorylation | NPEASSSTSVTPDVS CCCCCCCCCCCCCCC | 29.21 | 28857561 | |
| 364 | Phosphorylation | PEASSSTSVTPDVSD CCCCCCCCCCCCCCC | 26.41 | 24275569 | |
| 366 | Phosphorylation | ASSSTSVTPDVSDNE CCCCCCCCCCCCCCC | 17.34 | 16107342 | |
| 370 | Phosphorylation | TSVTPDVSDNEPDHY CCCCCCCCCCCCCCC | 41.94 | 16107342 | |
| 377 | Phosphorylation | SDNEPDHYRYSDTTD CCCCCCCCCCCCCCC | 20.73 | 23663014 | |
| 379 | Phosphorylation | NEPDHYRYSDTTDSD CCCCCCCCCCCCCCC | 12.06 | 20873877 | |
| 380 | Phosphorylation | EPDHYRYSDTTDSDP CCCCCCCCCCCCCCC | 21.34 | 16107342 | |
| 382 | Phosphorylation | DHYRYSDTTDSDPEN CCCCCCCCCCCCCCC | 26.94 | 21177249 | |
| 383 | Phosphorylation | HYRYSDTTDSDPENE CCCCCCCCCCCCCCC | 38.20 | 14976311 | |
| 385 | Phosphorylation | RYSDTTDSDPENEPF CCCCCCCCCCCCCCC | 53.63 | 22322096 | |
| 398 | Phosphorylation | PFDEDQHTQITKV-- CCCCCCCCCEECC-- | 18.94 | 20873877 | |
| 401 | Phosphorylation | EDQHTQITKV----- CCCCCCEECC----- | 18.88 | 12085208 | |
| 402 | Acetylation | DQHTQITKV------ CCCCCEECC------ | 47.80 | 18757404 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
| 27 | Y | Phosphorylation | Kinase | INSR | P06213 | PSP |
| 46 | Y | Phosphorylation | Kinase | SRC | P12931 | PSP |
| 68 | Y | Phosphorylation | Kinase | SRC | P12931 | PSP |
| 113 | S | Phosphorylation | Kinase | ATM | Q13315 | PSP |
| 155 | Y | Phosphorylation | Kinase | SRC | P12931 | PSP |
| 174 | Y | Phosphorylation | Kinase | INSR | P06213 | PSP |
| 174 | Y | Phosphorylation | Kinase | SRC | P12931 | PSP |
| 229 | S | Phosphorylation | Kinase | ROCK1 | Q13464 | PSP |
| 232 | T | Phosphorylation | Kinase | ROCK1 | Q13464 | PSP |
| 240 | Y | Phosphorylation | Kinase | FGFR3 | P22607 | PSP |
| 240 | Y | Phosphorylation | Kinase | FGFR2 | P21802 | PSP |
| 240 | Y | Phosphorylation | Kinase | SRC | P12931 | PSP |
| 240 | Y | Phosphorylation | Kinase | LCK | P06239 | PSP |
| 240 | Y | Phosphorylation | Kinase | LYN | P07948 | PSP |
| 315 | Y | Phosphorylation | Kinase | SRC | P12931 | PSP |
| 315 | Y | Phosphorylation | Kinase | LCK | P06239 | PSP |
| 336 | Y | Phosphorylation | Kinase | FRK | P42685 | Uniprot |
| 362 | S | Phosphorylation | Kinase | GSK3B | P49841 | PSP |
| 366 | T | Phosphorylation | Kinase | PLK3 | Q60806 | PSP |
| 366 | T | Phosphorylation | Kinase | PLK3 | Q9H4B4 | Uniprot |
| 366 | T | Phosphorylation | Kinase | CK2-FAMILY | - | GPS |
| 366 | T | Phosphorylation | Kinase | GSK3B | P49841 | PSP |
| 370 | S | Phosphorylation | Kinase | CK2 | - | Uniprot |
| 370 | S | Phosphorylation | Kinase | CK2-FAMILY | - | GPS |
| 370 | S | Phosphorylation | Kinase | PLK3 | Q60806 | PSP |
| 370 | S | Phosphorylation | Kinase | PLK3 | Q9H4B4 | Uniprot |
| 370 | S | Phosphorylation | Kinase | CSNK2A1 | P68400 | GPS |
| 377 | Y | Phosphorylation | Kinase | SRC | P12931 | PSP |
| 380 | S | Phosphorylation | Kinase | PLK1 | P53350 | PSP |
| 380 | S | Phosphorylation | Kinase | CK2 | - | Uniprot |
| 380 | S | Phosphorylation | Kinase | PRKCZ | Q05513 | GPS |
| 380 | S | Phosphorylation | Kinase | CSNK2A1 | P68400 | GPS |
| 380 | S | Phosphorylation | Kinase | ROCK1 | Q13464 | Uniprot |
| 380 | S | Phosphorylation | Kinase | STK11 | Q15831 | GPS |
| 382 | T | Phosphorylation | Kinase | ROCK1 | Q13464 | Uniprot |
| 382 | T | Phosphorylation | Kinase | PLK1 | P53350 | PSP |
| 382 | T | Phosphorylation | Kinase | CK2 | - | Uniprot |
| 382 | T | Phosphorylation | Kinase | PRKCZ | Q05513 | GPS |
| 382 | T | Phosphorylation | Kinase | STK11 | Q15831 | PhosphoELM |
| 382 | T | Phosphorylation | Kinase | CSNK2A1 | P68400 | GPS |
| 383 | T | Phosphorylation | Kinase | ROCK1 | Q13464 | Uniprot |
| 383 | T | Phosphorylation | Kinase | CSNK2A1 | P68400 | GPS |
| 383 | T | Phosphorylation | Kinase | CK2 | - | Uniprot |
| 383 | T | Phosphorylation | Kinase | STK11 | Q15831 | GPS |
| 383 | T | Phosphorylation | Kinase | PRKCZ | Q05513 | GPS |
| 383 | T | Phosphorylation | Kinase | PLK1 | P53350 | PSP |
| 385 | S | Phosphorylation | Kinase | CK2 | - | Uniprot |
| 385 | S | Phosphorylation | Kinase | CK2_GROUP | - | PhosphoELM |
| 385 | S | Phosphorylation | Kinase | CK2-FAMILY | - | GPS |
| 385 | S | Phosphorylation | Kinase | CSNK2A1 | P68400 | GPS |
| 398 | T | Phosphorylation | Kinase | ATM | Q13315 | PSP |
| - | K | Ubiquitination | E3 ubiquitin ligase | STUB1 | Q9UNE7 | PMID:26280536 |
| - | K | Ubiquitination | E3 ubiquitin ligase | NEDD4 | P46934 | PMID:17218260 |
| - | K | Ubiquitination | E3 ubiquitin ligase | XIAP | P98170 | PMID:22199232 |
| - | K | Ubiquitination | E3 ubiquitin ligase | SPOP | O43791 | PMID:24656772 |
| - | K | Ubiquitination | E3 ubiquitin ligase | WWP2 | O00308 | PMID:22199232 |
| - | K | Ubiquitination | E3 ubiquitin ligase | WWP1 | Q9H0M0 | PMID:31097636 |
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of PTEN_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| There are no disease associations of PTM sites. | ||||||
| OMIM Disease | ||||||
| 158350 | Cowden syndrome 1 (CWS1) | |||||
| 158350 | Lhermitte-Duclos disease (LDD) | |||||
| 153480 | Bannayan-Riley-Ruvalcaba syndrome (BRRS) | |||||
| 275355 | Squamous cell carcinoma of the head and neck (HNSCC) | |||||
| 608089 | Endometrial cancer (ENDMC) | |||||
| 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. | ||||||
| 613028 | ||||||
| 276950 | VACTERL association with hydrocephalus (VACTERL-H) | |||||
| 176807 | Prostate cancer (PC) | |||||
| 605309 | Macrocephaly/autism syndrome (MCEPHAS) | |||||
| Kegg Drug | ||||||
| There are no disease associations of PTM sites. | ||||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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| Acetylation | |
| Reference | PubMed |
| "Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6, AND MASS SPECTROMETRY. | |
| Phosphorylation | |
| Reference | PubMed |
| "Regulation of PTEN stability and activity by Plk3."; Xu D., Yao Y., Jiang X., Lu L., Dai W.; J. Biol. Chem. 285:39935-39942(2010). Cited for: PHOSPHORYLATION AT THR-366 AND SER-370, AND MUTAGENESIS OF THR-366 ANDSER-370. | |
| "Direct identification of PTEN phosphorylation sites."; Miller S., Lou D., Seldin D., Lane W., Neel B.; FEBS Lett. 528:145-153(2002). Cited for: PHOSPHORYLATION AT THR-366; SER-370 AND SER-385. | |
| "Threonine phosphorylation of the MMAC1/PTEN PDZ binding domain bothinhibits and stimulates PDZ binding."; Adey N.B., Huang L., Ormonde P.A., Baumgard M.L., Pero R.,Byreddy D.V., Tavtigian S.V., Bartel P.L.; Cancer Res. 60:35-37(2000). Cited for: INTERACTION WITH DLG1 AND MAST2, AND PHOSPHORYLATION AT THR-401. | |
| "Rak functions as a tumor suppressor by regulating PTEN proteinstability and function."; Yim E.-K., Peng G., Dai H., Hu R., Li K., Lu Y., Mills G.B.,Meric-Bernstam F., Hennessy B.T., Craven R.J., Lin S.-Y.; Cancer Cell 15:304-314(2009). Cited for: INTERACTION WITH FRK, PHOSPHORYLATION AT TYR-336, AND MUTAGENESIS OFTYR-336. | |
| Ubiquitylation | |
| Reference | PubMed |
| "The deubiquitinylation and localization of PTEN are regulated by aHAUSP-PML network."; Song M.S., Salmena L., Carracedo A., Egia A., Lo-Coco F.,Teruya-Feldstein J., Pandolfi P.P.; Nature 455:813-817(2008). Cited for: FUNCTION, INTERACTION WITH USP7, UBIQUITINATION AT LYS-13 AND LYS-289,DEUBIQUITINATION BY USP7, SUBCELLULAR LOCATION, AND MUTAGENESIS OFLYS-13 AND LYS-289. | |
