The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PHOSPHO1  -  phosphatase, orphan 1

Homo sapiens

Synonyms: Phosphoethanolamine/phosphocholine phosphatase
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PHOSPHO1


Psychiatry related information on PHOSPHO1


High impact information on PHOSPHO1

  • Altered growth factor responses in phospho-protein-driven signaling networks are crucial to cancer cell survival and pathology [1].
  • Thus, single cell measurements of phospho-protein responses reveal shifts in signaling potential of a phospho-protein network, allowing for categorizing of cell network phenotypes by multidimensional molecular profiles of signaling [1].
  • Expression of Ser(473) phospho Akt in primary human breast cancers statistically correlated with expression of p27 in tumor cytosol [11].
  • Immunostaining with phospho-specific antibodies in mammalian cells reveals mitotic phosphorylation of H3 Thr 3 in prophase and its dephosphorylation during anaphase [12].
  • Moesin is a widely expressed phospho-protein that links many transmembrane molecules to the cortical actin cytoskeleton [13].

Chemical compound and disease context of PHOSPHO1


Biological context of PHOSPHO1


Anatomical context of PHOSPHO1

  • PHOSPHO1 is a recently identified phosphatase expressed at high levels in the chicken growth plate and which may be involved in generating inorganic phosphate for skeletal matrix mineralization [20].
  • We isolated MVs from growth plate chondrocytes and confirmed the presence of high levels of PHOSPHO1 by immunoblotting [22].
  • Whole-mount in situ hybridization indicated that PHOSPHO1 expression occurred prior to E6.5 and was initially restricted to the bone collar within the mid-shaft of the diaphysis of long bones but by E11.5 expression was observed over the entire length of the diaphysis [22].
  • Ventricular ependymal cilia are crucial for directing cerebrospinal fluid flow, and ependyma of Tg mice exhibited disrupted cilia with increased phospho-CREB immunoreactivity [23].
  • The osmosensitivity of GAP43 furnishes a mechanistic framework that links axon elongation with phospho inositide metabolism, spontaneous triggering of cytosolic Ca(2+) transients and the regulation of actin dynamics and motility at the growth cone in response to temporal and local mechanical forces [24].

Associations of PHOSPHO1 with chemical compounds

  • PHOSPHO1, a phosphoethanolamine/phosphocholine phosphatase, is upregulated in mineralising cells and is thought to be involved in the generation of inorganic phosphate for bone mineralisation [21].
  • We show here that PHOSPHO1 exhibits high specific activities toward phosphoethanolamine (PEA) and phosphocholine (PCho) [25].
  • Alcian blue/alizarin red staining revealed that PHOSPHO1 expression seen in the primary regions of ossification preceded the deposition of mineral, suggesting that it is involved in the initial events of mineral formation [22].
  • Expression of PHOSPHO1, like TNAP activity, was found to be up-regulated in MVs isolated from chondrocytes induced to differentiate by the addition of ascorbic acid [22].
  • Phosphopeptide mapping identified a major autophosphorylation site, phospho (p)Thr-219, between the tandem C1 domains of the regulatory fragment in protein kinase C (PKC)theta [26].

Physical interactions of PHOSPHO1

  • A phospho-specific antibody was developed that only bound to full-length p21 protein after phosphorylation in vitro at Ser(146), and this reagent was further used to demonstrate that the inactive isoform of p21 recovered from Sf9 cells treated with phosphatase inhibitors had been phosphorylated in vivo at Ser(146) [27].
  • We found that the phospho-mimic mutation T341D increases binding with itself or the N-terminal half of ECT2 [28].
  • Mutational analyses and phospho-peptide mapping suggested that the SH2 domain of Csk may preferentially bind to ITIM Y562 of CD85j; yet, mutation to phenylalanine of Y533, Y614, and Y644 also significantly reduced Csk recruitment by CD85j [29].
  • Although phospho-dependent binding is important for Chk2 activity, previously uncharacterized phospho-independent FHA domain interactions appear to be the primary target of oncogenic lesions [30].
  • A native phospho-specific IgG binding assay was developed for quantitating the extent of p53 phosphorylation at Ser(315) where one, two, three, or four phosphates/tetramer could be defined after in vitro phosphorylation by cyclin-dependent protein kinases [31].

Enzymatic interactions of PHOSPHO1

  • Phospho amino acid analysis of the Mr 180,000 receptor band shows that only tyrosine residues are phosphorylated when A431 membranes are treated with either EGF or PMA [32].
  • Evidence was provided that GO/MGO upregulated MKP-1 activity that in turn dephosphorylated possibly co-aggregated phospho-ERK efficiently for inactivation [33].
  • Further, we examined the localization of the phosphorylated form of cofilin using phospho-specific antibody raised against phosphorylated cofilin [34].
  • METHODS: We examined the submembrane localization of NaPi-IIa in opossum kidney (OK-N2) cells that stably expressed human NaPi-IIa, and searched for a PTH-induced specific phosphorylating substrate on their membrane microdomains by immunoblotting with specific antibody against phospho substrates of protein kinases [35].
  • Interleukin-4/13 and transforming growth factor-beta-activated cells were identified by specific antibodies to phosphorylated (phospho-) signal transducer and activator of transcription 6 and phospho-Smad2, respectively [36].

Co-localisations of PHOSPHO1

  • HU and CAMPT treatment also led to the formation of RPA foci that co-localized with phospho-Nbs1 foci [37].

Regulatory relationships of PHOSPHO1

  • Addition of the inhibitor-of-protein serine/threonine phosphatases, okadaic acid, blocks the ATRA-mediated reduction in TGF-beta-induced phospho-Smad2 and shifts the differentiation toward monocytic end points [38].
  • However, the phospho-mimic mutation at T341 weakly stimulates the catalytic activity of ECT2 as detected by serum response element reporter gene assays [28].
  • In the present study, these claims have been explored by the genotyping of previously associated markers in CYP46A1 in three independent northern European case-control series encompassing 1323 individuals and including approximately 400 patients with measurements of CSF Abeta42 and phospho-tau protein levels [39].
  • The transient overexpression of TSP-1 up-regulated alpha2I collagen and phospho-Smad3 levels in normal fibroblasts but had no major effect on scleroderma fibroblasts [40].
  • The stabilized p53 in E7-expressing cells is in a wild-type conformation and the same number of phospho-forms is present [41].

Other interactions of PHOSPHO1


Analytical, diagnostic and therapeutic context of PHOSPHO1

  • Using a degenerate RT-PCR approach a fragment of human PHOSPHO1 was cloned [20].
  • Using a combination of in vitro kinase assay, Western blotting for phospho-specific proteins, pharmacologic inhibition, CCR5 knockout (CCR5Delta32) cells, and kinase-specific blocking peptide, we show for the first time that signaling through CCR5 in primary human macrophages is linked to the Src kinase Lyn [45].
  • Reductions of cellularity and numbers of Ki-67(+), phospho-Kit(+), phospho-kinase domain-containing receptor-positive (phospho-KDR(+)), phospho-signal transducer and activator of transcription 5-positive (phospho-STAT5(+)), and phospho-Akt(+) cells were detected in bone marrow histology analysis [46].
  • Here, we demonstrate that Akt phosphorylates the cell cycle inhibitory protein p21(Cip1) at Thr 145 in vitro and in intact cells as shown by in vitro kinase assays, site-directed mutagenesis, and phospho-peptide analysis [47].
  • Immunohistochemistry and immunofluorescence analysis of cortical sections was used to validate the microarray results and to probe the activity of mTOR in cytomegalic neurons using phospho-specific antibodies directed against known mTOR targets [48].


  1. Single cell profiling of potentiated phospho-protein networks in cancer cells. Irish, J.M., Hovland, R., Krutzik, P.O., Perez, O.D., Bruserud, Ø., Gjertsen, B.T., Nolan, G.P. Cell (2004) [Pubmed]
  2. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. Du, X.L., Edelstein, D., Dimmeler, S., Ju, Q., Sui, C., Brownlee, M. J. Clin. Invest. (2001) [Pubmed]
  3. Sustained IL-6/STAT-3 signaling in cholangiocarcinoma cells due to SOCS-3 epigenetic silencing. Isomoto, H., Mott, J.L., Kobayashi, S., Werneburg, N.W., Bronk, S.F., Haan, S., Gores, G.J. Gastroenterology (2007) [Pubmed]
  4. Effects of hypoxia on radiation-responsive stress-activated protein kinase, p53, and caspase 3 signals in TK6 human lymphoblastoid cells. Samuni, A.M., Kasid, U., Chuang, E.Y., Suy, S., Degraff, W., Krishna, M.C., Russo, A., Mitchell, J.B. Cancer Res. (2005) [Pubmed]
  5. Phosphorylation of Akt (Ser473) is an excellent predictor of poor clinical outcome in prostate cancer. Kreisberg, J.I., Malik, S.N., Prihoda, T.J., Bedolla, R.G., Troyer, D.A., Kreisberg, S., Ghosh, P.M. Cancer Res. (2004) [Pubmed]
  6. Localization of phosphorylated ERK/MAP kinases to mitochondria and autophagosomes in Lewy body diseases. Zhu, J.H., Guo, F., Shelburne, J., Watkins, S., Chu, C.T. Brain Pathol. (2003) [Pubmed]
  7. Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias. Riemenschneider, M., Wagenpfeil, S., Vanderstichele, H., Otto, M., Wiltfang, J., Kretzschmar, H., Vanmechelen, E., Förstl, H., Kurz, A. Mol. Psychiatry (2003) [Pubmed]
  8. Neuronal thread protein regulation and interaction with microtubule-associated proteins in SH-Sy5y neuronal cells. de la Monte, S.M., Chen, G.J., Rivera, E., Wands, J.R. Cell. Mol. Life Sci. (2003) [Pubmed]
  9. Levels of total tau and tau protein phosphorylated at threonine 181 in patients with incipient and manifest Alzheimer's disease. Schönknecht, P., Pantel, J., Hunt, A., Volkmann, M., Buerger, K., Hampel, H., Schröder, J. Neurosci. Lett. (2003) [Pubmed]
  10. Role of amygdala MAPK activation on immobility behavior of forced swim rats. Huang, T.Y., Lin, C.H. Behav. Brain Res. (2006) [Pubmed]
  11. PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. Shin, I., Yakes, F.M., Rojo, F., Shin, N.Y., Bakin, A.V., Baselga, J., Arteaga, C.L. Nat. Med. (2002) [Pubmed]
  12. The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment. Dai, J., Sultan, S., Taylor, S.S., Higgins, J.M. Genes Dev. (2005) [Pubmed]
  13. Exclusion of CD43 from the immunological synapse is mediated by phosphorylation-regulated relocation of the cytoskeletal adaptor moesin. Delon, J., Kaibuchi, K., Germain, R.N. Immunity (2001) [Pubmed]
  14. Paclitaxel induces inactivation of p70 S6 kinase and phosphorylation of Thr421 and Ser424 via multiple signaling pathways in mitosis. Le, X.F., Hittelman, W.N., Liu, J., McWatters, A., Li, C., Mills, G.B., Bast, R.C. Oncogene (2003) [Pubmed]
  15. Dual and opposing roles of ERK in regulating G(1) and S-G(2)/M delays in A549 cells caused by hyperoxia. Ko, J.C., Wang, Y.T., Yang, J.L. Exp. Cell Res. (2004) [Pubmed]
  16. Isoelectrofocusing of erythrocyte galactose 1 phospho uridyl transferase in a family with both galactosemia and Duarte variants. Schapira, F., Gregori, C., Banroques, J., Vidailhet, M., Despoisses, S., Vigneron, C. Hum. Genet. (1979) [Pubmed]
  17. A short leucine-rich sequence in the Borna disease virus p10 protein mediates association with the viral phospho- and nucleoproteins. Wolff, T., Pfleger, R., Wehner, T., Reinhardt, J., Richt, J.A. J. Gen. Virol. (2000) [Pubmed]
  18. Evidence that breast cancer associated microcalcifications are mineralized malignant cells. Castronovo, V., Bellahcene, A. Int. J. Oncol. (1998) [Pubmed]
  19. Comparative modelling of human PHOSPHO1 reveals a new group of phosphatases within the haloacid dehalogenase superfamily. Stewart, A.J., Schmid, R., Blindauer, C.A., Paisey, S.J., Farquharson, C. Protein Eng. (2003) [Pubmed]
  20. Chromosomal localization of the chicken and mammalian orthologues of the orphan phosphatase PHOSPHO1 gene. Houston, B., Paton, I.R., Burt, D.W., Farquharson, C. Anim. Genet. (2002) [Pubmed]
  21. Probing the substrate specificities of human PHOSPHO1 and PHOSPHO2. Roberts, S.J., Stewart, A.J., Schmid, R., Blindauer, C.A., Bond, S.R., Sadler, P.J., Farquharson, C. Biochim. Biophys. Acta (2005) [Pubmed]
  22. The presence of PHOSPHO1 in matrix vesicles and its developmental expression prior to skeletal mineralization. Stewart, A.J., Roberts, S.J., Seawright, E., Davey, M.G., Fleming, R.H., Farquharson, C. Bone (2006) [Pubmed]
  23. Expression of the human PAC1 receptor leads to dose-dependent hydrocephalus-related abnormalities in mice. Lang, B., Song, B., Davidson, W., MacKenzie, A., Smith, N., McCaig, C.D., Harmar, A.J., Shen, S. J. Clin. Invest. (2006) [Pubmed]
  24. GAP43 stimulates inositol trisphosphate-mediated calcium release in response to hypotonicity. Caprini, M., Gomis, A., Cabedo, H., Planells-Cases, R., Belmonte, C., Viana, F., Ferrer-Montiel, A. EMBO J. (2003) [Pubmed]
  25. Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities. Roberts, S.J., Stewart, A.J., Sadler, P.J., Farquharson, C. Biochem. J. (2004) [Pubmed]
  26. Critical role of novel Thr-219 autophosphorylation for the cellular function of PKCtheta in T lymphocytes. Thuille, N., Heit, I., Fresser, F., Krumböck, N., Bauer, B., Leuthaeusser, S., Dammeier, S., Graham, C., Copeland, T.D., Shaw, S., Baier, G. EMBO J. (2005) [Pubmed]
  27. Reversible phosphorylation at the C-terminal regulatory domain of p21(Waf1/Cip1) modulates proliferating cell nuclear antigen binding. Scott, M.T., Morrice, N., Ball, K.L. J. Biol. Chem. (2000) [Pubmed]
  28. Cytokinesis regulator ECT2 changes its conformation through phosphorylation at Thr-341 in G2/M phase. Hara, T., Abe, M., Inoue, H., Yu, L.R., Veenstra, T.D., Kang, Y.H., Lee, K.S., Miki, T. Oncogene (2006) [Pubmed]
  29. Recruitment of C-terminal Src kinase by the leukocyte inhibitory receptor CD85j. Sayós, J., Martínez-Barriocanal, A., Kitzig, F., Bellón, T., López-Botet, M. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  30. Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2. Li, J., Williams, B.L., Haire, L.F., Goldberg, M., Wilker, E., Durocher, D., Yaffe, M.B., Jackson, S.P., Smerdon, S.J. Mol. Cell (2002) [Pubmed]
  31. Stoichiometric phosphorylation of human p53 at Ser315 stimulates p53-dependent transcription. Blaydes, J.P., Luciani, M.G., Pospisilova, S., Ball, H.M., Vojtesek, B., Hupp, T.R. J. Biol. Chem. (2001) [Pubmed]
  32. Phorbol esters potentiate tyrosine phosphorylation of epidermal growth factor receptors in A431 membranes by a calcium-independent mechanism. Moon, S.O., Palfrey, H.C., King, A.C. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  33. Glyoxal and methylglyoxal induce lyoxal and methyglyoxal induce aggregation and inactivation of ERK in human endothelial cells. Akhand, A.A., Hossain, K., Kato, M., Miyata, T., Du, J., Suzuki, H., Kurokawa, K., Nakashima, I. Free Radic. Biol. Med. (2001) [Pubmed]
  34. Suppression of cofilin phosphorylation in insulin-stimulated ruffling membrane formation in KB cells. Arai, H., Atomi, Y. Cell Struct. Funct. (2003) [Pubmed]
  35. Role of membrane microdomains in PTH-mediated down-regulation of NaPi-IIa in opossum kidney cells. Nashiki, K., Taketani, Y., Takeichi, T., Sawada, N., Yamamoto, H., Ichikawa, M., Arai, H., Miyamoto, K., Takeda, E. Kidney Int. (2005) [Pubmed]
  36. Acute allergen-induced airway remodeling in atopic asthma. Phipps, S., Benyahia, F., Ou, T.T., Barkans, J., Robinson, D.S., Kay, A.B. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
  37. DNA lesion-specific co-localization of the Mre11/Rad50/Nbs1 (MRN) complex and replication protein A (RPA) to repair foci. Robison, J.G., Lu, L., Dixon, K., Bissler, J.J. J. Biol. Chem. (2005) [Pubmed]
  38. Levels of phospho-Smad2/3 are sensors of the interplay between effects of TGF-beta and retinoic acid on monocytic and granulocytic differentiation of HL-60 cells. Cao, Z., Flanders, K.C., Bertolette, D., Lyakh, L.A., Wurthner, J.U., Parks, W.T., Letterio, J.J., Ruscetti, F.W., Roberts, A.B. Blood (2003) [Pubmed]
  39. Variants of CYP46A1 may interact with age and APOE to influence CSF Abeta42 levels in Alzheimer's disease. Johansson, A., Katzov, H., Zetterberg, H., Feuk, L., Johansson, B., Bogdanovic, N., Andreasen, N., Lenhard, B., Brookes, A.J., Pedersen, N.L., Blennow, K., Prince, J.A. Hum. Genet. (2004) [Pubmed]
  40. Constitutive thrombospondin-1 overexpression contributes to autocrine transforming growth factor-beta signaling in cultured scleroderma fibroblasts. Mimura, Y., Ihn, H., Jinnin, M., Asano, Y., Yamane, K., Tamaki, K. Am. J. Pathol. (2005) [Pubmed]
  41. Stabilization and functional impairment of the tumor suppressor p53 by the human papillomavirus type 16 E7 oncoprotein. Eichten, A., Westfall, M., Pietenpol, J.A., Münger, K. Virology (2002) [Pubmed]
  42. Mitotic regulation of the human anaphase-promoting complex by phosphorylation. Kraft, C., Herzog, F., Gieffers, C., Mechtler, K., Hagting, A., Pines, J., Peters, J.M. EMBO J. (2003) [Pubmed]
  43. Specific down-regulation of interleukin-12 signaling through induction of phospho-STAT4 protein degradation. Wang, K.S., Zorn, E., Ritz, J. Blood (2001) [Pubmed]
  44. Glycogen synthase kinase 3 phosphorylates RBL2/p130 during quiescence. Litovchick, L., Chestukhin, A., DeCaprio, J.A. Mol. Cell. Biol. (2004) [Pubmed]
  45. The Src kinase Lyn is required for CCR5 signaling in response to MIP-1beta and R5 HIV-1 gp120 in human macrophages. Tomkowicz, B., Lee, C., Ravyn, V., Cheung, R., Ptasznik, A., Collman, R.G. Blood (2006) [Pubmed]
  46. A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease. Fiedler, W., Serve, H., Döhner, H., Schwittay, M., Ottmann, O.G., O'Farrell, A.M., Bello, C.L., Allred, R., Manning, W.C., Cherrington, J.M., Louie, S.G., Hong, W., Brega, N.M., Massimini, G., Scigalla, P., Berdel, W.E., Hossfeld, D.K. Blood (2005) [Pubmed]
  47. Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and proliferation of endothelial cells. Rössig, L., Jadidi, A.S., Urbich, C., Badorff, C., Zeiher, A.M., Dimmeler, S. Mol. Cell. Biol. (2001) [Pubmed]
  48. Activation of mammalian target of rapamycin in cytomegalic neurons of human cortical dysplasia. Ljungberg, M.C., Bhattacharjee, M.B., Lu, Y., Armstrong, D.L., Yoshor, D., Swann, J.W., Sheldon, M., D'Arcangelo, G. Ann. Neurol. (2006) [Pubmed]
WikiGenes - Universities