ID  Q9WTR8;
PN  PH domain leucine-rich repeat protein phosphatase 1;
GN  Phlpp1;
OS  10116;
SL  Nucleus Position: SL-0178;
SL  Nucleus Position: SL-0182;
SL  Comments: Cytoplasm {ECO:0000269|PubMed:12594205}. Membrane {ECO:0000269|PubMed:12594205}; Peripheral membrane protein {ECO:0000269|PubMed:12594205}. [Isoform 1]: Cytoplasm {ECO:0000269|PubMed:20819118}. Cell membrane {ECO:0000269|PubMed:20819118}. [Isoform 2]: Nucleus, nucleoplasm {ECO:0000269|PubMed:20819118}. Nucleus membrane {ECO:0000269|PubMed:20819118}. Cytoplasm {ECO:0000269|PubMed:20819118}. Cell membrane {ECO:0000269|PubMed:20819118}.
DR  UNIPROT: Q9WTR8;
DR  Pfam: PF13516;
DR  Pfam: PF13855;
DR  Pfam: PF00169;
DR  Pfam: PF00481;
DR  PROSITE: PS51450;
DR  PROSITE: PS50003;
DR  PROSITE: PS51746;
DE  Function: Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (PubMed:20819118). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons while isoform 1 may promote Akt and PKC activation and inhibit ERK signaling (PubMed:20819118). Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (By similarity). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (By similarity). Inhibits cancer cell proliferation and may act as a tumor suppressor (By similarity). Dephosphorylates RAF1 inhibiting its kinase activity (By similarity). May act as a negative regulator of K-Ras signaling in membrane rafts (PubMed:12594205). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T-cells (By similarity). {ECO:0000250|UniProtKB:O60346, ECO:0000250|UniProtKB:Q8CHE4, ECO:0000269|PubMed:12594205, ECO:0000269|PubMed:20819118}.
DE  Reference Proteome: Yes;
DE  Interaction: O14745; IntAct: EBI-11165272; Score: 0.40
GO  GO:0005737;
GO  GO:0043231;
GO  GO:0031965;
GO  GO:0005654;
GO  GO:0005886;
GO  GO:0046872;
GO  GO:0017018;
GO  GO:0004722;
GO  GO:0006915;
GO  GO:0007623;
GO  GO:0009649;
GO  GO:0021766;
GO  GO:0070373;
GO  GO:0051898;
GO  GO:0090038;
GO  GO:0051897;
GO  GO:0090037;
GO  GO:0006470;
GO  GO:0042981;
GO  GO:0046328;
GO  GO:0043408;
GO  GO:1900744;
GO  GO:0001932;
GO  GO:0002667;
GO  GO:0007165;
TP  Membrane Topology: Peripheral; Source: UniProt - Experimental Evidence {ECO:0000269|PubMed:12594205};
SQ  MEPAAAAPAQRLADPTGEDRAPAAAAAAEGGRSPDSVLSAAAPSGGNGGAAREEAPCEAPPGPLPGRAGGTGRRRRRGVP
SQ  QPAAGGAAPVTAAGGGANSLLLRRGRLKRNLSAAASSSSSPSSASSAAGGLPASCSASASLCTRSLDRKTLLQKHRQLLQ
SQ  LQPSDRDWVRHQLQRGCVHVFDRHMASSYLRPVLCTLDTTAAEVAARLLQLGHKGGGVVKVLGHGPPPAAAPAASDQTPA
SQ  TELGRDVEPPPSSSTVGAVRGPARAPPADLPLPGGAWTRCAPRVNPAPSDSSPGELFAGGPCSPSRAPRPASDTESFSLS
SQ  PSAESVSDRLDPYSSGGGSSSSSEELEADPATVLTGPSGPPHHPVRSSQPRPPSPKTSALLQPKAPTGVDGTGLVVGEGP
SQ  GDDKAVAAAAPGVPLWTPGRIRETVQKTSSPPSLYVQLHGETTRRLEADEKPLQIQNDYLFQLGFGELWRVQEEGMDSEI
SQ  GCLIRFYAGKPHSTGSSERIQLSGMYNVRKGKMQLPVNRWTRRQVILCGTCLIVSSVKDSSSGKMHVLPLIGGKVEEVKK
SQ  HQHCLAFSSSGPQSQTYYICFDTFTEYLRWLRQVSKVASQRISSVDLSCCSLEHLPANLFYSQDLTHLNLKQNFLRQNPS
SQ  LPAARGLGELQRFTKLKSLNLSNNHLGAFPSAVCSIPTLAELNVSCNALQEVPAAVGAMQNLQTFLLDGNFLQSLPAELE
SQ  NMHQLSYLGLSFNEFTDIPEVLEKLTAVDKLCMAGNCMETLRLQALRRMPHIKHVDLRLNILRKLITDEVDFLQHVTQLD
SQ  LRDNKLGDLDAMIFNNIEVLHCERNQLVTLNICGYFLKALYASSNELVQLDVYPVPNYLSYMDVSRNCLESVPEWVCESR
SQ  KLEVLDIGHNQICELPARLFCNSSLRKLLAGHNRLARLPERLERTSVEVLDVQHNQIIELPPNLLMKADSLRFLNASANK
SQ  LETLPPATLSEETSSILQELYLTNNSLTDKCVPLLTGHPRLKILHMAYNRLQSFPASKMAKLEELEEIDISGNKLKAIPT
SQ  TIMNCRRMHTVIAHSNCIEVFPEVMQLPEVKCVDLSCNELSEITLPENLPPKLQELDLTGNPRLALDHKSLELLNNIRCF
SQ  KIDQPSAGDASGAPAVWSHGYTEASGVKNKLCVAALSVNNFRDNREALYGVFDGDRNVEVPYLLQCTMSDILAEELQKTK
SQ  NEEEYMVNTFIVMQRKLGTAGQKLGGAAVLCHIRHDPVDLGGSFTLTSANVGKCQTVLCRNGKPLSLSRSYTMSCEEERK
SQ  RIKQHKAIITEDGKVNGVTESTRILGYTFLHPSVVPRPHVQSVLLTPQDEFFILGSKGLWDSLSIEEAVEAVRNVPDALA
SQ  AAKKLCTLAQSYGCHDSISAVVVQLSVTEDSFCCCELSVGGSMPPPSPGIFPPSVSMVIKDRPSDGLGVPSSSSGMASEI
SQ  SSELSTSEMSSEVGSTASDEPPSGALSESSPAYPSEQRCMLHPVCLSNSFQRQLSSATFSSAFSDNGLDSDDEEPIEGVF
SQ  SNGSRVEVEVDIHCSRAKEKERQQHLLQVPAEASDEGIVISANEDESGLSKKTDISAVGTIGRRRANGSVPPQERSHNVI
SQ  EVATDAPLRKPGGYFAAPAQPDPDDQFIIPPELEEEVKEIMKHHQEQQQQQQQQQQQQQQQPPPPPQPPQAQAQAQAQAQ
SQ  RPFQMDHLPDCYDTPL
//