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Gene Review

Phgdh  -  3-phosphoglycerate dehydrogenase

Mus musculus

Synonyms: 3-PGDH, 3PGDH, 4930479N23, A10, D-3-phosphoglycerate dehydrogenase, ...
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Disease relevance of Phgdh

  • Using Western blotting with ZF5 and sera of autoimmune disease, we detected one serum, named M6 serum, which contains the antibody against a transcriptional repressor ZF5 [1].
  • Sera from pigs naturally infected with B. hyodysenteriae also reacted with recombinant BmpB expressed in E. coli [2].
  • This phenomenon was demonstrated in lymphocytes and lymphoma cells treated with anti-H-2 sera; spleen lymphocytes treated with concanavalin A or anti-immunoglobulin antibodies, and VSV-infected mouse fibroblast line MC57 treated with antiserum against viral antigens [3].
  • Antiserum raised against PKF and sera from rabbits bearing rous sarcoma virus (RSV)-induced tumors quantitatively precipitate the same 60 kd phosphoprotein from cell lysates of three different RSV-transformed cell lines [4].
  • BPAG1 is the major antigenic determinant of autoimmune sera of bullous pemphigoid (BP) patients [5].

Psychiatry related information on Phgdh

  • Sera from mice with 8-wk Schistosoma mansoni infection, chronic (20-wk infection) moderate splenomegaly syndrome (MSS), or chronic hypersplenomegaly syndrome (HSS) were passed over an S. mansoni soluble egg antigen (SEA) immunoaffinity column to prepare Ids (8WkId, MSS Id, HSS Id) [6].
  • The latency period before the original paraprotein was detected in the sera of recipients varied in different experiments between 1 and 9 months after transplantation [7].

High impact information on Phgdh

  • Antibodies to DNA and nucleoproteins are found in sera of individuals with systemic autoimmune disease [8].
  • In addition deficient mice produce antibody to mouse C5 when injected with sera from C5 sufficient (normal) strains [9].
  • Mouse T-cell surface glycoprotein recognised by heterologous anti-thymocyte sera and its relationship to Thy-1 antigen [10].
  • Thymus reactive IgM autoantibodies in normal mouse sera [11].
  • This mechanism is dependent on the signaling pathway intermediary myeloid differentiation factor 88 (MyD88), such that neither IL-1R nor MyD88-deficient mice developed visually detectable synovitis after transfer of arthritogenic sera [12].

Chemical compound and disease context of Phgdh

  • The tumor necrosis-inducing factor (TNF) found in sera of Corynebacterium parvum-treated, endotoxin-stressed BALB/C and outbred albino CD-1 mice has been purified to a single band of protein by polyacrylamide gel electrophoresis after identification and removal of contaminating albumin and transferrin [13].
  • The tyrosine-specific protein kinase activity previously described in T-antigens of polyoma virus immunoprecipitated with anti-tumour sera has been investigated using monoclonal antibodies [14].
  • Molecular differences between dopamine (DA) neurons may explain why the mesostriatal DA neurons in the A9 region preferentially degenerate in Parkinson's disease (PD) and toxic models, whereas the adjacent A10 region mesolimbic and mesocortical DA neurons are relatively spared [15].
  • Little or no precipitation of purified Rauscher murine leukemia virus Mr 70,000 glycoprotein was observed with sera of mice immunized with P815 cells [16].
  • First, we assessed the neutralizing potential of these antibodies in C57BL/6 mice under acute septic shock by measuring IL-1beta in sera 4 h after lipopolysaccharide injection [17].

Biological context of Phgdh

  • In the cerebral cortex of transgenic mouse embryos, the Phgdh promoter-LacZ transgene DNA containing -1,794/+4 promoter sequences directed beta-galactosidase (beta-Gal) expression mainly to Phgdh-positive neuroepithelium and radial glia [18].
  • Transient transfection analysis revealed that the cis-acting elements necessary for basal transcription of Phgdh are contained within the -196/+4 proximal sequence of the promoter, in which the conserved Sp1 recognition sites play an important role for basal promoter activity [19].
  • Although basal promoter activity of the gene appeared to depend on an Sp1 binding sequence residing between -193 and -184 in both glial and neuronal cultures, an upstream 5'-flanking region between -1,794 and -1,095 contributed to up-regulation of Phgdh transcription in a glial-cell-specific manner [18].
  • These observations suggest the presence of cis-acting elements that confer the cell type specificity of Phgdh transcription in the distal promoter region [18].
  • Structural analysis demonstrated that the Phgdh gene spans approximately 27 kilobases (kb) in length and comprises 12 exons with 11 intervening introns [19].

Anatomical context of Phgdh


Associations of Phgdh with chemical compounds

  • D-3-Phosphoglycerate dehydrogenase (Phgdh; EC is a necessary enzyme for de novo L-serine biosynthesis via the phosphorylated pathway [18].
  • The original activity was not restored readily by in vitro treatment of the sera with pyridoxal phosphate (PLP), in contrast to the rapid activation, by the same treatment, of apoAAT in the sera from control mice [23].
  • Sera of deficient mice lack detectable C5 activity and protein2,3 [9].
  • We found significantly increased amounts of both cytokines in the sera of CB3/LPS-treated mice compared with animals treated only with LPS [24].
  • Immunoprecipitation and polyacrylamide gel electrophoresis analysis of the molecules reactive with anti-Qa-1 and anti-37 sera show that the Qa-1 molecule of Qa-1b (Qa-1.2) mouse strains is identical to the product of gene 37 on the basis of molecular weight, pI, and strain distribution [25].

Regulatory relationships of Phgdh

  • In addition, 3PGDH was highly expressed throughout development in the olfactory ensheathing glia, a specialized supporting cell that thoroughly ensheathes olfactory nerves [26].

Other interactions of Phgdh

  • Anti-MBP and anti-GFAP, isotypes IgM and IgG, were measured in sera by ELISA on day 38 [27].
  • The preferential glial expression of ASCT1 was consistent with that of 3PGDH, and their extensive colocalization was demonstrated at the cellular level [28].
  • At early stages when the neural wall consists exclusively of the ventricular zone, neuroepithelial stem cells expressed 3PGDH strongly and homogeneously [26].

Analytical, diagnostic and therapeutic context of Phgdh

  • Specificity of the antibodies was established by immunoblotting against sera and brain homogenates of wild type and apoE-deficient mice [29].
  • To investigate whether such a metabolic neuron-glial relationship is fundamental to the developing and adult brain, we examined by in situ hybridization and immunohistochemistry the cellular expression of 3-phosphoglycerate dehydrogenase (3PGDH), the initial step enzyme for de novo l-serine biosynthesis in animal cells [26].
  • A clone with little H-2Dd (10-15% lysable) was tumorigenic even after treatment with anti-H-2Dd sera; at least 50% of the tumor cells were lysed by anti-H-2Dd [30].
  • Analysis by immunoprecipitation shows that the viral capsid protein is part of the active nucleoprotein complex, but recognition of the complex by only a subset of anti-capsid sera implies that the protein is constrained conformationally [31].
  • Examination of sera from infected mice revealed autoantibodies that, by immunofluorescence, reacted with cytoplasmic antigens in the islets of Langerhans, anterior pituitary, and gastric mucosa of uninfected mice [32].


  1. Identification of human autoantibodies to the transcriptional repressor ZF5. Yanagidani, A., Matsuoka, M., Yokoro, K., Tanaka, H., Numoto, M. J. Autoimmun. (2000) [Pubmed]
  2. Identification of the gene encoding BmpB, a 30 kDa outer envelope lipoprotein of Brachyspira (Serpulina) hyodysenteriae, and immunogenicity of recombinant BmpB in mice and pigs. Lee, B.J., La, T., Mikosza, A.S., Hampson, D.J. Vet. Microbiol. (2000) [Pubmed]
  3. The participation of alpha-actinin in the capping of cell membrane components. Geiger, B., Singer, S.J. Cell (1979) [Pubmed]
  4. A mouse homolog to the avian sarcoma virus src protein is a member of a protein kinase cascade. Spector, M., Pepinsky, R.B., Vogt, V.M., Racker, E. Cell (1981) [Pubmed]
  5. Gene targeting of BPAG1: abnormalities in mechanical strength and cell migration in stratified epithelia and neurologic degeneration. Guo, L., Degenstein, L., Dowling, J., Yu, Q.C., Wollmann, R., Perman, B., Fuchs, E. Cell (1995) [Pubmed]
  6. Neonatal idiotypic exposure alters subsequent cytokine, pathology, and survival patterns in experimental Schistosoma mansoni infections. Montesano, M.A., Colley, D.G., Eloi-Santos, S., Freeman, G.L., Secor, W.E. J. Exp. Med. (1999) [Pubmed]
  7. Idiopathic paraproteinemia. II. Transplantation of the paraprotein-producing clone from old to young C57BL/KaLwRij mice. Radl, J., De Glopper, E.D., Schuit, H.R., Zurcher, C. J. Immunol. (1979) [Pubmed]
  8. The site and stage of anti-DNA B-cell deletion. Chen, C., Nagy, Z., Radic, M.Z., Hardy, R.R., Huszar, D., Camper, S.A., Weigert, M. Nature (1995) [Pubmed]
  9. Genetic defect in secretion of complement C5 in mice. Ooi, Y.M., Colten, H.R. Nature (1979) [Pubmed]
  10. Mouse T-cell surface glycoprotein recognised by heterologous anti-thymocyte sera and its relationship to Thy-1 antigen. Trowbridge, I.S., Weissman, I.L., Bevan, M.J. Nature (1975) [Pubmed]
  11. Thymus reactive IgM autoantibodies in normal mouse sera. Martin, W.J., Martin, S.E. Nature (1975) [Pubmed]
  12. Interleukin 1 receptor dependence of serum transferred arthritis can be circumvented by toll-like receptor 4 signaling. Choe, J.Y., Crain, B., Wu, S.R., Corr, M. J. Exp. Med. (2003) [Pubmed]
  13. Murine tumor necrosis-inducing factor: purification and effects on myelomonocytic leukemia cells. Green, S., Dobrjansky, A., Chiasson, M.A. J. Natl. Cancer Inst. (1982) [Pubmed]
  14. Protein kinase activities associated with distinct antigenic forms of polyoma virus middle T-antigen. Dilworth, S.M. EMBO J. (1982) [Pubmed]
  15. Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection. Chung, C.Y., Seo, H., Sonntag, K.C., Brooks, A., Lin, L., Isacson, O. Hum. Mol. Genet. (2005) [Pubmed]
  16. Expression of type C viral glycoproteins on P815 cells: higher expression of Mr 70,000 glycoprotein-containing glycoprotein on immunogenic variants. Jacquemin, P.C. Cancer Res. (1982) [Pubmed]
  17. Treatment with neutralizing antibodies specific for IL-1beta prevents cyclophosphamide-induced diabetes in nonobese diabetic mice. Cailleau, C., Diu-Hercend, A., Ruuth, E., Westwood, R., Carnaud, C. Diabetes (1997) [Pubmed]
  18. Functional analysis of mouse 3-phosphoglycerate dehydrogenase (Phgdh) gene promoter in developing brain. Shimizu, M., Furuya, S., Shinoda, Y., Mitoma, J., Okamura, T., Miyoshi, I., Kasai, N., Hirabayashi, Y., Suzuki, Y. J. Neurosci. Res. (2004) [Pubmed]
  19. Mouse 3-phosphoglycerate dehydrogenase gene: genomic organization, chromosomal localization, and promoter analysis. Mitoma, J., Furuya, S., Shimizu, M., Shinoda, Y., Yoshida, K., Azuma, N., Tanaka, H., Suzuki, Y., Hirabayashi, Y. Gene (2004) [Pubmed]
  20. Targeted disruption of the mouse 3-phosphoglycerate dehydrogenase gene causes severe neurodevelopmental defects and results in embryonic lethality. Yoshida, K., Furuya, S., Osuka, S., Mitoma, J., Shinoda, Y., Watanabe, M., Azuma, N., Tanaka, H., Hashikawa, T., Itohara, S., Hirabayashi, Y. J. Biol. Chem. (2004) [Pubmed]
  21. Increase in anti-astrocyte antibodies in the serum of guinea pigs during active stages of experimental autoimmune encephalomyelitis. Pekovic, D., Raine, C.S., Traugott, U. J. Neuroimmunol. (1990) [Pubmed]
  22. Astrocytic cell clones derived from established cultures of 8-day postnatal mouse cerebella. Alliot, F., Pessac, B. Brain Res. (1984) [Pubmed]
  23. Inhibition of serum aspartate aminotransferase induced by isoniazid administration in mice. Yamada, R.H., Wakabayashi, Y., Iwashima, A. Acta Vitaminol. Enzymol. (1984) [Pubmed]
  24. Interleukin 1 or tumor necrosis factor can promote Coxsackie B3-induced myocarditis in resistant B10.A mice. Lane, J.R., Neumann, D.A., Lafond-Walker, A., Herskowitz, A., Rose, N.R. J. Exp. Med. (1992) [Pubmed]
  25. The TL region gene 37 encodes a Qa-1 antigen. Wolf, P.R., Cook, R.G. J. Exp. Med. (1990) [Pubmed]
  26. 3-Phosphoglycerate dehydrogenase, a key enzyme for l-serine biosynthesis, is preferentially expressed in the radial glia/astrocyte lineage and olfactory ensheathing glia in the mouse brain. Yamasaki, M., Yamada, K., Furuya, S., Mitoma, J., Hirabayashi, Y., Watanabe, M. J. Neurosci. (2001) [Pubmed]
  27. Lead alters the immunogenicity of two neural proteins: a potential mechanism for the progression of lead-induced neurotoxicity. Waterman, S.J., el-Fawal, H.A., Snyder, C.A. Environ. Health Perspect. (1994) [Pubmed]
  28. Neutral amino acid transporter ASCT1 is preferentially expressed in L-Ser-synthetic/storing glial cells in the mouse brain with transient expression in developing capillaries. Sakai, K., Shimizu, H., Koike, T., Furuya, S., Watanabe, M. J. Neurosci. (2003) [Pubmed]
  29. Apolipoprotein E is found in astrocytes but not in microglia in the normal mouse brain. Fujita, S.C., Sakuta, K., Tsuchiya, R., Hamanaka, H. Neurosci. Res. (1999) [Pubmed]
  30. Abelson virus-transformed lymphocytes: null cells that modulate H-2. Pratt, D.M., Strominger, J., Parkman, R., Kaplan, D., Schwaber, J., Rosenberg, N., Scher, C.D. Cell (1977) [Pubmed]
  31. A nucleoprotein complex mediates the integration of retroviral DNA. Bowerman, B., Brown, P.O., Bishop, J.M., Varmus, H.E. Genes Dev. (1989) [Pubmed]
  32. Virus-induced diabetes mellitus. XX. Polyendocrinopathy and autoimmunity. Onodera, T., Toniolo, A., Ray, U.R., Jenson, A.B., Knazek, R.A., Notkins, A.L. J. Exp. Med. (1981) [Pubmed]
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