| Identification |
|---|
| HMDB Protein ID
| HMDBP14121 |
| Secondary Accession Numbers
| None |
| Name
| Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase daf-18 |
| Synonyms
|
- Abnormal dauer formation protein 18
|
| Gene Name
| DAF-18 |
| Protein Type
| Unknown |
| Biological Properties |
|---|
| General Function
| Not Available |
| Specific Function
| Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins (By similarity). Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate (PubMed:15637588). By dephosphorylating PtdIns(3,4,5)P3 antagonizes PtdIns(3,4,5)P3 production by age-1/PI3K and thus, negatively regulates daf-2-mediated processes including dauer formation, longevity, fat metabolism, chemotaxis towards salt, thermotolerance and axon guidance (PubMed:9885576, PubMed:10209098, PubMed:10377431, PubMed:16950159, PubMed:19249087, PubMed:23995781, PubMed:10077613, PubMed:20207731). Similarly, promotes apoptosis during embryonic development by suppressing the recruitment of the prosurvival kinases akt-1/2 to the plasma membrane (PubMed:25383666). In addition, regulates Z2/Z3 germline precursor cell cycle by maintaining them arrested at the G2 stage and by controlling their growth during L1 diapause (PubMed:16631584). After sperm depletion in larvae and adult hermaphrodites, promotes germline stem cell quiescence and oocyte accumulation (PubMed:26552888). By dephosphorylating ephrin-like receptor vab-1 on tyrosine residues, negatively regulates oocyte maturation downstream of vab-1 and upstream of mpk-1, independently of daf-2 (PubMed:19853560). Plays a role in postembryonic muscle arm extensions (PubMed:18436204). Required for neurite outgrowth during AIY interneuron embryonic development (PubMed:22069193). Mainly independently of daf-2, negatively regulates vulva induction probably by inhibiting mpk-1 phosphorylation (PubMed:22916028). Both lipid and protein phosphatase activities are required for the regulation of vulva induction (PubMed:22916028). |
| Pathways
|
- Autophagy - animal
- Axon regeneration
- FoxO signaling pathway
- Inositol phosphate metabolism
- Longevity regulating pathway - worm
- mTOR signaling pathway
- Phosphatidylinositol signaling system
|
| Reactions
| Not Available |
| GO Classification
|
| Biological Process |
| learning or memory |
| determination of adult lifespan |
| response to heat |
| regulation of chemotaxis |
| chemotaxis |
| phosphatidylinositol dephosphorylation |
| positive regulation of positive chemotaxis |
| phosphatidylinositol 3-kinase signaling |
| negative regulation of cell proliferation |
| cell motility |
| chemosensory behavior |
| dauer larval development |
| positive regulation of dauer larval development |
| regulation of protein kinase B signaling |
| response to salt |
| protein import into nucleus |
| dephosphorylation |
| protein dephosphorylation |
| Cellular Component |
| cytosol |
| cell projection |
| plasma membrane |
| dendrite |
| nucleus |
| internal side of plasma membrane |
| perikaryon |
| neuronal cell body |
| axon |
| Molecular Function |
| phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity |
| lipid binding |
| protein serine phosphatase activity |
| protein threonine phosphatase activity |
| protein tyrosine phosphatase activity |
|
| Cellular Location
|
Not Available
|
| Gene Properties |
|---|
| Chromosome Location
| Not Available |
| Locus
| Not Available |
| SNPs
| Not Available |
| Gene Sequence
|
Not Available
|
| Protein Properties |
|---|
| Number of Residues
| 962 |
| Molecular Weight
| 110328.245 |
| Theoretical pI
| 6.84 |
| Pfam Domain Function
|
|
| Signals
|
Not Available
|
|
Transmembrane Regions
|
Not Available
|
| Protein Sequence
|
Not Available
|
| External Links |
|---|
| GenBank ID Protein
| Not Available |
| UniProtKB/Swiss-Prot ID
| G5EE01 |
| UniProtKB/Swiss-Prot Entry Name
| PTEN_CAEEL |
| PDB IDs
|
Not Available |
| GenBank Gene ID
| Not Available |
| GeneCard ID
| Not Available |
| GenAtlas ID
| Not Available |
| HGNC ID
| Not Available |
| References |
|---|
| General References
| - Authors unspecified: Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998 Dec 11;282(5396):2012-8. doi: 10.1126/science.282.5396.2012. [PubMed:9851916 ]
- Ogg S, Ruvkun G: The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway. Mol Cell. 1998 Dec;2(6):887-93. doi: 10.1016/s1097-2765(00)80303-2. [PubMed:9885576 ]
- Rouault JP, Kuwabara PE, Sinilnikova OM, Duret L, Thierry-Mieg D, Billaud M: Regulation of dauer larva development in Caenorhabditis elegans by daf-18, a homologue of the tumour suppressor PTEN. Curr Biol. 1999 Mar 25;9(6):329-32. doi: 10.1016/s0960-9822(99)80143-2. [PubMed:10209098 ]
- Gil EB, Malone Link E, Liu LX, Johnson CD, Lees JA: Regulation of the insulin-like developmental pathway of Caenorhabditis elegans by a homolog of the PTEN tumor suppressor gene. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2925-30. doi: 10.1073/pnas.96.6.2925. [PubMed:10077613 ]
- Solari F, Bourbon-Piffaut A, Masse I, Payrastre B, Chan AM, Billaud M: The human tumour suppressor PTEN regulates longevity and dauer formation in Caenorhabditis elegans. Oncogene. 2005 Jan 6;24(1):20-7. doi: 10.1038/sj.onc.1207978. [PubMed:15637588 ]
- Fukuyama M, Rougvie AE, Rothman JH: C. elegans DAF-18/PTEN mediates nutrient-dependent arrest of cell cycle and growth in the germline. Curr Biol. 2006 Apr 18;16(8):773-9. doi: 10.1016/j.cub.2006.02.073. [PubMed:16631584 ]
- Suzuki Y, Han M: Genetic redundancy masks diverse functions of the tumor suppressor gene PTEN during C. elegans development. Genes Dev. 2006 Feb 15;20(4):423-8. doi: 10.1101/gad.1378906. [PubMed:16481471 ]
- Dixon SJ, Alexander M, Chan KK, Roy PJ: Insulin-like signaling negatively regulates muscle arm extension through DAF-12 in Caenorhabditis elegans. Dev Biol. 2008 Jun 1;318(1):153-61. doi: 10.1016/j.ydbio.2008.03.019. Epub 2008 Mar 20. [PubMed:18436204 ]
- Brisbin S, Liu J, Boudreau J, Peng J, Evangelista M, Chin-Sang I: A role for C. elegans Eph RTK signaling in PTEN regulation. Dev Cell. 2009 Oct;17(4):459-69. doi: 10.1016/j.devcel.2009.08.009. [PubMed:19853560 ]
- Padmanabhan S, Mukhopadhyay A, Narasimhan SD, Tesz G, Czech MP, Tissenbaum HA: A PP2A regulatory subunit regulates C. elegans insulin/IGF-1 signaling by modulating AKT-1 phosphorylation. Cell. 2009 Mar 6;136(5):939-51. doi: 10.1016/j.cell.2009.01.025. Epub 2009 Feb 26. [PubMed:19249087 ]
- Palmitessa A, Benovic JL: Arrestin and the multi-PDZ domain-containing protein MPZ-1 interact with phosphatase and tensin homolog (PTEN) and regulate Caenorhabditis elegans longevity. J Biol Chem. 2010 May 14;285(20):15187-15200. doi: 10.1074/jbc.M110.104612. Epub 2010 Mar 5. [PubMed:20207731 ]
- Christensen R, de la Torre-Ubieta L, Bonni A, Colon-Ramos DA: A conserved PTEN/FOXO pathway regulates neuronal morphology during C. elegans development. Development. 2011 Dec;138(23):5257-67. doi: 10.1242/dev.069062. [PubMed:22069193 ]
- Nakdimon I, Walser M, Frohli E, Hajnal A: PTEN negatively regulates MAPK signaling during Caenorhabditis elegans vulval development. PLoS Genet. 2012;8(8):e1002881. doi: 10.1371/journal.pgen.1002881. Epub 2012 Aug 16. [PubMed:22916028 ]
- Liu J, Visser-Grieve S, Boudreau J, Yeung B, Lo S, Chamberlain G, Yu F, Sun T, Papanicolaou T, Lam A, Yang X, Chin-Sang I: Insulin activates the insulin receptor to downregulate the PTEN tumour suppressor. Oncogene. 2014 Jul 17;33(29):3878-85. doi: 10.1038/onc.2013.347. Epub 2013 Sep 2. [PubMed:23995781 ]
- Narbonne P, Maddox PS, Labbe JC: DAF-18/PTEN locally antagonizes insulin signalling to couple germline stem cell proliferation to oocyte needs in C. elegans. Development. 2015 Dec 15;142(24):4230-41. doi: 10.1242/dev.130252. Epub 2015 Nov 9. [PubMed:26552888 ]
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