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PHLPP1

Gene
PHLPP1
Protein
PH domain leucine-rich repeat-containing protein phosphatase 1
Organism
Homo sapiens
Length
1717 amino acids
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:15808505, PubMed:17386267, PubMed:18162466). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). 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 (PubMed:18162466). Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). 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).
Mass
184.672 kDa
Sequence
MEPAAAATVQRLPELGREDRASAPAAAAAAAAAAAAAAAALAAAAGGGRSPEPALTPAAPSGGNGSGSGAREEAPGEAPPGPLPGRAGGAGRRRRRGAPQPIAGGAAPVPGAGGGANSLLLRRGRLKRNLSAAAAAASSSSSSSAAAASHSPGAAGLPASCSASASLCTRSLDRKTLLLKHRQTLQLQPSDRDWVRHQLQRGCVHVFDRHMASTYLRPVLCTLDTTAGEVAARLLQLGHKGGGVVKVLGQGPGAAAAREPAEPPPEAGPRLAPPEPRDSEVPPARSAPGAFGGPPRAPPADLPLPVGGPGGWSRRASPAPSDSSPGEPFVGGPVSSPRAPRPVVSDTESFSLSPSAESVSDRLDPYSSGGGSSSSSEELEADAASAPTGVPGQPRRPGHPAQPLPLPQTASSPQPQQKAPRAIDSPGGAVREGSCEEKAAAAVAPGGLQSTPGRSGVTAEKAPPPPPPPTLYVQLHGETTRRLEAEEKPLQIQNDYLFQLGFGELWRVQEEGMDSEIGCLIRFYAGKPHSTGSSERIQLSGMYNVRKGKMQLPVNRWTRRQVILCGTCLIVSSVKDSLTGKMHVLPLIGGKVEEVKKHQHCLAFSSSGPQSQTYYICFDTFTEYLRWLRQVSKVASQRISSVDLSCCSLEHLPANLFYSQDLTHLNLKQNFLRQNPSLPAARGLNELQRFTKLKSLNLSNNHLGDFPLAVCSIPTLAELNVSCNALRSVPAAVGVMHNLQTFLLDGNFLQSLPAELENMKQLSYLGLSFNEFTDIPEVLEKLTAVDKLCMSGNCVETLRLQALRKMPHIKHVDLRLNVIRKLIADEVDFLQHVTQLDLRDNKLGDLDAMIFNNIEVLHCERNQLVTLDICGYFLKALYASSNELVQLDVYPVPNYLSYMDVSRNRLENVPEWVCESRKLEVLDIGHNQICELPARLFCNSSLRKLLAGHNQLARLPERLERTSVEVLDVQHNQLLELPPNLLMKADSLRFLNASANKLESLPPATLSEETNSILQELYLTNNSLTDKCVPLLTGHPHLKILHMAYNRLQSFPASKMAKLEELEEIDLSGNKLKAIPTTIMNCRRMHTVIAHSNCIEVFPEVMQLPEIKCVDLSCNELSEVTLPENLPPKLQELDLTGNPRLVLDHKTLELLNNIRCFKIDQPSTGDASGAPAVWSHGYTEASGVKNKLCVAALSVNNFCDNREALYGVFDGDRNVEVPYLLQCTMSDILAEELQKTKNEEEYMVNTFIVMQRKLGTAGQKLGGAAVLCHIKHDPVDPGGSFTLTSANVGKCQTVLCRNGKPLPLSRSYIMSCEEELKRIKQHKAIITEDGKVNGVTESTRILGYTFLHPSVVPRPHVQSVLLTPQDEFFILGSKGLWDSLSVEEAVEAVRNVPDALAAAKKLCTLAQSYGCHDSISAVVVQLSVTEDSFCCCELSAGGAVPPPSPGIFPPSVNMVIKDRPSDGLGVPSSSSGMASEISSELSTSEMSSEVGSTASDEPPPGALSENSPAYPSEQRCMLHPICLSNSFQRQLSSATFSSAFSDNGLDSDDEEPIEGVFTNGSRVEVEVDIHCSRAKEKEKQQHLLQVPAEASDEGIVISANEDEPGLPRKADFSAVGTIGRRRANGSVAPQERSHNVIEVATDAPLRKPGGYFAAPAQPDPDDQFIIPPELEEEVKEIMKHHQEQQQQQQPPPPPQLQPQLPRHYQLDQLPDYYDTPL

Gene
Phlpp1
Protein
PH domain leucine-rich repeat protein phosphatase 1
Organism
Rattus norvegicus
Length
1696 amino acids
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).
Mass
183.364 kDa
Sequence
MEPAAAAPAQRLADPTGEDRAPAAAAAAEGGRSPDSVLSAAAPSGGNGGAAREEAPCEAPPGPLPGRAGGTGRRRRRGVPQPAAGGAAPVTAAGGGANSLLLRRGRLKRNLSAAASSSSSPSSASSAAGGLPASCSASASLCTRSLDRKTLLQKHRQLLQLQPSDRDWVRHQLQRGCVHVFDRHMASSYLRPVLCTLDTTAAEVAARLLQLGHKGGGVVKVLGHGPPPAAAPAASDQTPATELGRDVEPPPSSSTVGAVRGPARAPPADLPLPGGAWTRCAPRVNPAPSDSSPGELFAGGPCSPSRAPRPASDTESFSLSPSAESVSDRLDPYSSGGGSSSSSEELEADPATVLTGPSGPPHHPVRSSQPRPPSPKTSALLQPKAPTGVDGTGLVVGEGPGDDKAVAAAAPGVPLWTPGRIRETVQKTSSPPSLYVQLHGETTRRLEADEKPLQIQNDYLFQLGFGELWRVQEEGMDSEIGCLIRFYAGKPHSTGSSERIQLSGMYNVRKGKMQLPVNRWTRRQVILCGTCLIVSSVKDSSSGKMHVLPLIGGKVEEVKKHQHCLAFSSSGPQSQTYYICFDTFTEYLRWLRQVSKVASQRISSVDLSCCSLEHLPANLFYSQDLTHLNLKQNFLRQNPSLPAARGLGELQRFTKLKSLNLSNNHLGAFPSAVCSIPTLAELNVSCNALQEVPAAVGAMQNLQTFLLDGNFLQSLPAELENMHQLSYLGLSFNEFTDIPEVLEKLTAVDKLCMAGNCMETLRLQALRRMPHIKHVDLRLNILRKLITDEVDFLQHVTQLDLRDNKLGDLDAMIFNNIEVLHCERNQLVTLNICGYFLKALYASSNELVQLDVYPVPNYLSYMDVSRNCLESVPEWVCESRKLEVLDIGHNQICELPARLFCNSSLRKLLAGHNRLARLPERLERTSVEVLDVQHNQIIELPPNLLMKADSLRFLNASANKLETLPPATLSEETSSILQELYLTNNSLTDKCVPLLTGHPRLKILHMAYNRLQSFPASKMAKLEELEEIDISGNKLKAIPTTIMNCRRMHTVIAHSNCIEVFPEVMQLPEVKCVDLSCNELSEITLPENLPPKLQELDLTGNPRLALDHKSLELLNNIRCFKIDQPSAGDASGAPAVWSHGYTEASGVKNKLCVAALSVNNFRDNREALYGVFDGDRNVEVPYLLQCTMSDILAEELQKTKNEEEYMVNTFIVMQRKLGTAGQKLGGAAVLCHIRHDPVDLGGSFTLTSANVGKCQTVLCRNGKPLSLSRSYTMSCEEERKRIKQHKAIITEDGKVNGVTESTRILGYTFLHPSVVPRPHVQSVLLTPQDEFFILGSKGLWDSLSIEEAVEAVRNVPDALAAAKKLCTLAQSYGCHDSISAVVVQLSVTEDSFCCCELSVGGSMPPPSPGIFPPSVSMVIKDRPSDGLGVPSSSSGMASEISSELSTSEMSSEVGSTASDEPPSGALSESSPAYPSEQRCMLHPVCLSNSFQRQLSSATFSSAFSDNGLDSDDEEPIEGVFSNGSRVEVEVDIHCSRAKEKERQQHLLQVPAEASDEGIVISANEDESGLSKKTDISAVGTIGRRRANGSVPPQERSHNVIEVATDAPLRKPGGYFAAPAQPDPDDQFIIPPELEEEVKEIMKHHQEQQQQQQQQQQQQQQQPPPPPQPPQAQAQAQAQAQRPFQMDHLPDCYDTPL

Gene
Phlpp1
Protein
PH domain leucine-rich repeat-containing protein phosphatase 1
Organism
Mus musculus
Length
1687 amino acids
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 (By similarity). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). 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. Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation. Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylates RAF1 inhibiting its kinase activity. May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (PubMed:17382888). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (PubMed:20080691). Involved in development and function of regulatory T-cells (PubMed:21498666).
Mass
182.367 kDa
Sequence
MEPAAAAPAQRLADPTGEDQALAAAAAEGGRCPDPALSAAAPSGGNGGAAREEAPCEAPPGPLPGRAGGTGRRRRRGAPQPAAGGAAPVPAAGGGANSLLLKRGRLKRNLSAAAAASSSSSPSSASSAAGGLPASCSASASLCTRSLDRKTLLLKHRQLLQLQPSDRDWVRHQLQRGCVHVFDRHMASSYLRPVLCTLDTTAAEVAARLLQLGHKGGGVVKVLGYGPPPAAAPAASDQTLDGEHGRDVEPPPSSGTVGAVRGPARAPPADLPLPGGAWTRCAPRISPAPSDSSPGELFAGGPGSPPRAPRPASDTESFSLSPSAESVSDRLDPYSSGGGGSSSSSEELEADPAMPHRPGRPAQPRPPSPKTSALLQPKAPTGVDSTGVIAGEGPGDDKAMAAAAPDVPLSTSGRIRETVQKTSPPSLYVQLHGETTRRLEADEKPLQIQNDYLFQLGFGELWRVQEEGMDSEIGCLIRFYAGKPHSTGSSERIQLSGMYNVRKGKMQLPVNRWTRRQVILCGTCLIVSSVKDSVSGKMHVLPLIGGKVEEVKKHQHCLAFSSSGPQSQTYYICFDTFTEYLRWLRQVSKVASQRISSVDLSCCSLEHLPANLFYSQDLTHLNLKQNFLRQTPTLPAARGLGELQRFTKLKSLNLSNNHLGAFPSAVCSIPTLAELNVSCNALREVPAAVGDMQNLQTFLLDGNFLQSLPAELESMHQLSYLGLSFNEFTDIPEVLEKLTAVDKLCMAGNCVETLRLQALRRMPHIKHVDLRLNILRKLMADEVDFVQHVTQLDLRDNKLGDLDAMIFNNIEVLHCERNQLVTLNVCGYFLKALYASSNELAQLDVYPVPNYLSYMDVSRNCLESVPEWVCESRKLEVLDIGHNQICELPARLFCNSSLRKLLAGHNRLARLPERLERTSVEVLDVQHNQITELPPNLLMKADSLRFLNASANKLETLPPATLSEETSSILQELYLTNNCLTDKCVPLLTGHPRLKILHMAYNRLQSFPASKMAKLEELEEIDISGNKLKAIPTTIMNCRRMHTVIAHSNCIEVFPEVMQLPEVKCVDLSCNELSEITLPENLPPKLQELDLTGNPRLALDHKSLELLNNIRCFKIDQPSAGDASGAPAVWSHGYTEASGVKNKLCVAALSVNNFRDNREALYGVFDGDRNVEVPYLLQCTMSDILAEELQKTKNEEEYMVNTFIVMQRKLGTAGQKLGGAAVLCHIKPDPVDLGGSFTLTSANVGKCQTVLCRNGKPLSLSRSYIMSCEEERKRIKQHKAIITEDGKVNGVTESTRILGYTFLHPSVVPRPHVQSVLLTPQDEFFILGSKGLWDSLSIDEAVEAVRNVPDALAAAKKLCTLAQSYGCHDSISAVVVQLSVTEDSFCCCELSAGGSMPPPSPGIFPPSVNMVIKDRPSDGLGVPSSSSGMASEISSELSTSEMSSEVGSTASDEPPSGVLNESSPAYPNEQRCMLHPVCLSNSFQRQLSSATFSSAFSDNGLDSDDEEPIEGVFSNGSRVEVEVDIHCSRAKEKERQQHLLQVPAEASDEGIVISANEDESGLSKKADFSAVGTIGRRRANGSVAPQERSHNVIEVAADAPLRKPGGYFAAPAQPDPDDQFIIPPELEEEVKEIMKHHQEQQQQQQQQQLPPPPQPPQPQPQPQPQPQPQPQRHFQMDHLPDCYDTPL