Protein: PH domain leucine-rich repeat protein phosphatase 1 (EC 3.1.3.16) (Pleckstrin homology domain-containing family E member 1) (PH domain-containing family E member 1) (Suprachiasmatic nucleus circadian oscillatory protein) (Q9WTR8)
Organism: Rattus norvegicus (Rat)
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. 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. 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. 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).
Subcellular location: Cytoplasm {ECO:0000269|PubMed:12594205}. Membrane {ECO:0000269|PubMed:12594205}; Peripheral membrane protein {ECO:0000269|PubMed:12594205}.; SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm {ECO:0000269|PubMed:20819118}. Cell membrane {ECO:0000269|PubMed:20819118}.; SUBCELLULAR LOCATION: [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}.
Interaction partners:
- RAC-alpha serine/threonine-protein kinase
- RAC-beta serine/threonine-protein kinase
- RAC-gamma serine/threonine-protein kinase
- PH domain leucine-rich repeat-containing protein phosphatase 2
- peptidylprolyl isomerase
- Ubiquitin carboxyl-terminal hydrolase 46
- Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
- Ubiquitin carboxyl-terminal hydrolase 1
- Adenylyl cyclase-associated protein 2
- Adenylyl cyclase-associated protein 1
Sequence:
MEPAAAAPAQRLADPTGEDRAPAAAAAAEGGRSPDSVLSAAAPSGGNGGAAREEAPCEAPPGPLPGRAGGTGRRRRRGVPQPAAGGAAPVTAAGGGANSLLLRRGRLKRNLSAAASSSSSPSSASSAAGGLPASCSASASLCTRSLDRKTLLQKHRQLLQLQPSDRDWVRHQLQRGCVHVFDRHMASSYLRPVLCTLDTTAAEVAARLLQLGHKGGGVVKVLGHGPPPAAAPAASDQTPATELGRDVEPPPSSSTVGAVRGPARAPPADLPLPGGAWTRCAPRVNPAPSDSSPGELFAGGPCSPSRAPRPASDTESFSLSPSAESVSDRLDPYSSGGGSSSSSEELEADPATVLTGPSGPPHHPVRSSQPRPPSPKTSALLQPKAPTGVDGTGLVVGEGPGDDKAVAAAAPGVPLWTPGRIRETVQKTSSPPSLYVQLHGETTRRLEADEKPLQIQNDYLFQLGFGELWRVQEEGMDSEIGCLIRFYAGKPHSTGSSERIQLSGMYNVRKGKMQLPVNRWTRRQVILCGTCLIVSSVKDSSSGKMHVLPLIGGKVEEVKKHQHCLAFSSSGPQSQTYYICFDTFTEYLRWLRQVSKVASQRISSVDLSCCSLEHLPANLFYSQDLTHLNLKQNFLRQNPSLPAARGLGELQRFTKLKSLNLSNNHLGAFPSAVCSIPTLAELNVSCNALQEVPAAVGAMQNLQTFLLDGNFLQSLPAELENMHQLSYLGLSFNEFTDIPEVLEKLTAVDKLCMAGNCMETLRLQALRRMPHIKHVDLRLNILRKLITDEVDFLQHVTQLDLRDNKLGDLDAMIFNNIEVLHCERNQLVTLNICGYFLKALYASSNELVQLDVYPVPNYLSYMDVSRNCLESVPEWVCESRKLEVLDIGHNQICELPARLFCNSSLRKLLAGHNRLARLPERLERTSVEVLDVQHNQIIELPPNLLMKADSLRFLNASANKLETLPPATLSEETSSILQELYLTNNSLTDKCVPLLTGHPRLKILHMAYNRLQSFPASKMAKLEELEEIDISGNKLKAIPTTIMNCRRMHTVIAHSNCIEVFPEVMQLPEVKCVDLSCNELSEITLPENLPPKLQELDLTGNPRLALDHKSLELLNNIRCFKIDQPSAGDASGAPAVWSHGYTEASGVKNKLCVAALSVNNFRDNREALYGVFDGDRNVEVPYLLQCTMSDILAEELQKTKNEEEYMVNTFIVMQRKLGTAGQKLGGAAVLCHIRHDPVDLGGSFTLTSANVGKCQTVLCRNGKPLSLSRSYTMSCEEERKRIKQHKAIITEDGKVNGVTESTRILGYTFLHPSVVPRPHVQSVLLTPQDEFFILGSKGLWDSLSIEEAVEAVRNVPDALAAAKKLCTLAQSYGCHDSISAVVVQLSVTEDSFCCCELSVGGSMPPPSPGIFPPSVSMVIKDRPSDGLGVPSSSSGMASEISSELSTSEMSSEVGSTASDEPPSGALSESSPAYPSEQRCMLHPVCLSNSFQRQLSSATFSSAFSDNGLDSDDEEPIEGVFSNGSRVEVEVDIHCSRAKEKERQQHLLQVPAEASDEGIVISANEDESGLSKKTDISAVGTIGRRRANGSVPPQERSHNVIEVATDAPLRKPGGYFAAPAQPDPDDQFIIPPELEEEVKEIMKHHQEQQQQQQQQQQQQQQQPPPPPQPPQAQAQAQAQAQRPFQMDHLPDCYDTPL