Protein: Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase daf-18 (EC 3.1.3.16) (EC 3.1.3.48) (EC 3.1.3.67) (Abnormal dauer formation protein 18) (G5EE01)
Organism: Caenorhabditis elegans
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. 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. Similarly, promotes apoptosis during embryonic development by suppressing the recruitment of the prosurvival kinases akt-1/2 to the plasma membrane. 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. After sperm depletion in larvae and adult hermaphrodites, promotes germline stem cell quiescence and oocyte accumulation. 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. Plays a role in postembryonic muscle arm extensions. Required for neurite outgrowth during AIY interneuron embryonic development. Mainly independently of daf-2, negatively regulates vulva induction probably by inhibiting mpk-1 phosphorylation. Both lipid and protein phosphatase activities are required for the regulation of vulva induction. Plays a role in gonad and germline development following the L1 diapause.
Subcellular location: Perikaryon {ECO:0000269|PubMed:22069193}. Cell membrane {ECO:0000269|PubMed:22916028}; Peripheral membrane protein {ECO:0000269|PubMed:22916028}. Cell projection, axon {ECO:0000269|PubMed:22069193}. Cell projection, dendrite {ECO:0000269|PubMed:22069193}. Cytoplasm {ECO:0000269|PubMed:22916028}. Nucleus {ECO:0000269|PubMed:22916028}. Note=During vulva development, localizes to the cytoplasm and the nucleus of vulva precursor cells and of vulva cells at the Pn.p stage of L2 larvae. From the Pn.px to Pn.pxx stage of L3/L4 larvae, localization increases at the plasma membrane and becomes maximal at the Pn.pxxx stage of L4 larvae. {ECO:0000269|PubMed:22916028}.
Interaction partners:
- DNA-dependent metalloprotease dvc-1
- Phosphatidylinositol 3-kinase age-1
- Forkhead box protein O
- Uncharacterized protein C05C10.5
- Phosphoinositide 3-kinase adapter subunit
- Insulin-like receptor
- Serine/threonine-protein kinase akt-1
- Serine/threonine-protein kinase akt-2
- Phosphatidylinositol 3-kinase catalytic subunit type 3
- Phosphatidylinositol-3-phosphatase SAC1
Sequence:
MVTPPPDVPSTSTRSMARDLQENPNRQPGEPRVSEPYHNSIVERIRHIFRTAVSSNRCRTEYQNIDLDCAYITDRIIAIGYPATGIEANFRNSKVQTQQFLTRRHGKGNVKVFNLRGGYYYDADNFDGNVICFDMTDHHPPSLELMAPFCREAKEWLEADDKHVIAVHCKAGKGRTGVMICALLIYINFYPSPRQILDYYSIIRTKNNKGVTIPSQRRYIYYYHKLRERELNYLPLRMQLIGVYVERPPKTWGGGSKIKVEVGNGSTILFKPDPLIISKSNHQRERATWLNNCDTPNEFDTGEQKYHGFVSKRAYCFMVPEDAPVFVEGDVRIDIREIGFLKKFSDGKIGHVWFNTMFACDGGLNGGHFEYVDKTQPYIGDDTSIGRKNGMRRNETPMRKIDPETGNEFESPWQIVNPPGLEKHITEEQAMENYTNYGMIPPRYTISKILHEKHEKGIVKDDYNDRKLPMGDKSYTESGKSGDIRGVGGPFEIPYKAEEHVLTFPVYEMDRALKSKDLNNGMKLHVVLRCVDTRDSKMMEKSEVFGNLAFHNESTRRLQALTQMNPKWRPEPCAFGSKGAEMHYPPSVRYSSNDGKYNGACSENLVSDFFEHRNIAVLNRYCRYFYKQRSTSRSRYPRKFRYCPLIKKHFYIPADTDDVDENGQPFFHSPEHYIKEQEKIDAEKAAKGIENTGPSTSGSSAPGTIKKTEASQSDKVKPATEDELPPARLPDNVRRFPVVGVDFENPEEESCEHKTVESIAGFEPLEHLFHESYHPNTAGNMLRQDYHTDSEVKIAEQEAKAFVDQLLNGQGVLQEFMKQFKVPSDNSFADYVTGQAEVFKAQIALLEQSEDFQRVQANAEEVDLEHTLGEAFERFGHVVEESNGSSKNPKALKTREQMVKETGKDTQKTRNHVLLHLEANHRVQIERRETCPELHPEDKIPRIAHFSENSFSDSNFDQAIYL