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Gene Review

PHLPP1  -  PH domain and leucine rich repeat protein...

Homo sapiens

Synonyms: KIAA0606, PH domain leucine-rich repeat-containing protein phosphatase 1, PH domain-containing family E member 1, PHLPP, PLEKHE1, ...
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Disease relevance of PHLPP


High impact information on PHLPP


Biological context of PHLPP

  • Doing so involves an all-vs.-all comparison of protein domains [taken here from the Structural Classification of Proteins (scop) database] and then fitting a simple distribution function to the observed scores [6].
  • Our tree is largely in agreement with results from the structural classification of proteins (SCOP), a multidimensional classification based on homologous sequences, full three-dimensional structure, information about chemistry and evolution, and human judgment [7].
  • We find 783 out of the 859 superfamilies in SCOP in these genomes, and the 783 families occur in 1307 pairwise combinations [8].
  • Analysis of CATH and SCOP revealed the significant contribution that structural genomics is making to the coverage of superfamilies and folds [9].
  • However, 50 cases were identified in which SCOP domains are disrupted in the middle by alternative splicing [10].

Anatomical context of PHLPP

  • SCOP, a novel gene product expressed in a circadian manner in rat suprachiasmatic nucleus [11].
  • Soils and plant parts belonging to Thymus praecox Opiz., Acinos alpinus (L.) Moench, Plantago holosteum Scop and Festuca punctoria Sm species collected from three directions around Wolfram Mine Work were used for our investigations [12].
  • Neurosecretory cells in the brain, ventral ganglia, and retrocerebral endocrine glands aortal complex of a milkweed bug, Lygaeus pandurus Scop. have been described using a variety of techniques in whole mounts and sections [13].
  • Behavioral studies in rats have demonstrated that the medial septum/diagonal band of Broca (MSDB), which sends cholinergic and GABAergic projections to the hippocampus, is a critical locus in mediating the amnesic effects of atr/scop [14].

Associations of PHLPP with chemical compounds

  • The Sequence Alignment Benchmark (SABmark) provides sets of multiple alignment problems derived from the SCOP classification [15].
  • Effect of bioactive compounds from Sainfoin ( Onobrychis viciifolia Scop.) on the in vitro larval migration of Haemonchus contortus: role of tannins and flavonol glycosides [16].
  • From these results, we suggest that the attenuating effect of luteolin (10 mg/kg, i.p.) on the deficits of passive avoidance performance induced by SCOP may be related to the increases in the activities of central muscarinic and nicotinic receptors [17].
  • The effects of phorate and some of its metabolites incorporated in an artificial diet on liquid uptake by Aphis fabae scop [18].
  • Luteolin was not reversed by scopolamine N-methylbromide (M-SCOP) but blocked the impairment of learning acquisition induced by cholinergic neurotoxin (ethylcholine aziridinium, AF64A) and muscarinic (scopolamine hydrobromide, SCOP) and nicotinic (mecamylamine, MECA) receptor antagonists [17].
  • Knockdown of PHLPP expression reduces the rate of phorbol ester-triggered dephosphorylation of the hydrophobic motif, but not turn motif, of PKC alpha [19].

Analytical, diagnostic and therapeutic context of PHLPP

  • We use the Structural Classification of Proteins (SCOP) database to link sequence alignments from the SMART and Pfam databases [20].
  • Structure and sequence analysis of several metal-binding proteins reveals unexpected similarities in structural domains classified as different protein folds in SCOP and suggests unification of seven folds that belong to two protein classes [21].
  • Micellar electrokinetic chromatography (MEKC) was used for the separation and determination of two iridoid glycosides, aucubin and catalpol, in several Plantago species growing in Croatia: P. altissima L., P. argentea Chaix, P. coronopus L., P. holosteum Scop [22].


  1. PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. Gao, T., Furnari, F., Newton, A.C. Mol. Cell (2005) [Pubmed]
  2. Transderm Scop for prevention of motion sickness. Johnson, P., Hansen, D., Matarazzo, D., Petterson, L., Swisher, C., Trappolini, A. N. Engl. J. Med. (1984) [Pubmed]
  3. Structural genomics analysis: characteristics of atypical, common, and horizontally transferred folds. Hegyi, H., Lin, J., Greenbaum, D., Gerstein, M. Proteins (2002) [Pubmed]
  4. Proteolytic Degradation of SCOP in the Hippocampus Contributes to Activation of MAP Kinase and Memory. Shimizu, K., Phan, T., Mansuy, I.M., Storm, D.R. Cell (2007) [Pubmed]
  5. PHLPP and a Second Isoform, PHLPP2, Differentially Attenuate the Amplitude of Akt Signaling by Regulating Distinct Akt Isoforms. Brognard, J., Sierecki, E., Gao, T., Newton, A.C. Mol. Cell (2007) [Pubmed]
  6. A unified statistical framework for sequence comparison and structure comparison. Levitt, M., Gerstein, M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  7. A protein taxonomy based on secondary structure. Przytycka, T., Aurora, R., Rose, G.D. Nat. Struct. Biol. (1999) [Pubmed]
  8. Domain combinations in archaeal, eubacterial and eukaryotic proteomes. Apic, G., Gough, J., Teichmann, S.A. J. Mol. Biol. (2001) [Pubmed]
  9. Progress of structural genomics initiatives: an analysis of solved target structures. Todd, A.E., Marsden, R.L., Thornton, J.M., Orengo, C.A. J. Mol. Biol. (2005) [Pubmed]
  10. Alternative splice variants encoding unstable protein domains exist in the human brain. Homma, K., Kikuno, R.F., Nagase, T., Ohara, O., Nishikawa, K. J. Mol. Biol. (2004) [Pubmed]
  11. SCOP, a novel gene product expressed in a circadian manner in rat suprachiasmatic nucleus. Shimizu, K., Okada, M., Takano, A., Nagai, K. FEBS Lett. (1999) [Pubmed]
  12. Investigation of influence of tungsten mine wastes on the elemental composition of some alpine and subalpine plants on Mount Uludağ, Bursa, Turkey. Güleryüz, G., Arslan, H., Kirmizi, S., Güçer, S. Environ. Pollut. (2002) [Pubmed]
  13. Neurosecretion in the milkweed bug, Lygaeus pandurus scop. (Heteroptera: Lygaeidae). Awasthi, V.B. Journal für Hirnforschung. (1980) [Pubmed]
  14. Muscarinic tone sustains impulse flow in the septohippocampal GABA but not cholinergic pathway: implications for learning and memory. Alreja, M., Wu, M., Liu, W., Atkins, J.B., Leranth, C., Shanabrough, M. J. Neurosci. (2000) [Pubmed]
  15. SABmark--a benchmark for sequence alignment that covers the entire known fold space. Van Walle, I., Lasters, I., Wyns, L. Bioinformatics (2005) [Pubmed]
  16. Effect of bioactive compounds from Sainfoin ( Onobrychis viciifolia Scop.) on the in vitro larval migration of Haemonchus contortus: role of tannins and flavonol glycosides. Barrau, E., Fabre, N., Fouraste, I., Hoste, H. Parasitology (2005) [Pubmed]
  17. Effects of luteolin on learning acquisition in rats: Involvement of the central cholinergic system. Tsai, F.S., Peng, W.H., Wang, W.H., Wu, C.R., Hsieh, C.C., Lin, Y.T., Feng, I.C., Hsieh, M.T. Life Sci. (2007) [Pubmed]
  18. The effects of phorate and some of its metabolites incorporated in an artificial diet on liquid uptake by Aphis fabae scop. Ho, S.H. Toxicol. Lett. (1983) [Pubmed]
  19. The phosphatase PHLPP controls the cellular levels of protein kinase C. Gao, T., Brognard, J., Newton, A.C. J. Biol. Chem. (2008) [Pubmed]
  20. Structural similarity to link sequence space: new potential superfamilies and implications for structural genomics. Aloy, P., Oliva, B., Querol, E., Aviles, F.X., Russell, R.B. Protein Sci. (2002) [Pubmed]
  21. Treble clef finger--a functionally diverse zinc-binding structural motif. Grishin, N.V. Nucleic Acids Res. (2001) [Pubmed]
  22. Determination of aucubin and catalpol in Plantago species by micellar electrokinetic chromatography. Jurisić, R., Debeljak, Z., Vladimir-Knezević, S., Vuković, J. Z. Naturforsch., C, J. Biosci. (2004) [Pubmed]
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