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Gene Review

PDC  -  phosducin

Homo sapiens

Synonyms: 33 kDa phototransducing protein, MEKA, PHD, PhLOP, PhLP, ...
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Disease relevance of PDC


Psychiatry related information on PDC


High impact information on PDC

  • SMCX bound H3K9me3 via its N-terminal PHD (plant homeodomain) finger, which may help coordinate H3K4 demethylation and H3K9 methylation in transcriptional repression [9].
  • The gene product (PHF11) contains two PHD zinc fingers and probably regulates transcription [10].
  • The murine gamma-herpesvirus-68 K3 (MK3) is a PHD/LAP finger protein that downregulates major histocompatibility complex (MHC) class I expression [11].
  • Inhibitor of growth protein-2 (ING2) is a nuclear adaptor protein that can regulate p53 and histone acetylation in response to cellular stress and contains a PHD (plant homeodomain) finger that can interact with phosphatidylinositol-5-phosphate (PtdIns5P) [12].
  • We also examined the phenotype, lymphokine profile, and V beta usage of PDC-specific T cell clones isolated from cellular infiltrates from the livers of PBC patients [13].

Chemical compound and disease context of PDC

  • These monoclonal antibodies, which are the first human monoclonal antibodies to pyruvate dehydrogenase complex generated from a patient with primary biliary cirrhosis, will be a valuable tool for studying the B-cell autoepitopes in PDC and the mechanism of autoantibody production in primary biliary cirrhosis [14].
  • L-glutamate per se was gliotoxic only at concentrations much higher than the maximum reached with the potent EAAT substrate inhibitor L-trans-pyrrolidine-2,4-dicarboxylate (PDC), and toxicity was lower [15].
  • The present results support the hypothesis that cycad consumption may be an important factor in the etiology of ALS-PDC and further suggest that some sterol glucosides may be involved in other neurodegenerative disorders [16].
  • 4. MAM alters gene expression in SY5Y human neuroblastoma cells and, in the presence of DNA damage and reduced DNA repair, enhances glutamate-modulated expression of tau mRNA in rat primary neurons; the corresponding protein (TAU) is elevated in ALS/PDC and Alzheimer's disease [17].
  • Thus in different cell types, isoform-specific patterns of PHD induction by hypoxia and estrogen alter both the relative abundance of the PHDs and their relative contribution to the regulation of HIF [18].

Biological context of PDC


Anatomical context of PDC


Associations of PDC with chemical compounds

  • Accordingly, a glutathione S-transferase-fusion protein containing only the amino-terminal 105 amino acids of phosducin displayed G beta gamma binding ability [23].
  • Calcium current inhibition after short-term exposure to norepinephrine was minimally altered by PDC or PDCL expression [27].
  • The genotoxicant methylazoxymethanol (MAM) is a widely used developmental neurotoxin, and its glucoside is an etiological factor for western Pacific amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS/PDC) [28].
  • An immunoprecipitation assay also showed that the ciliate phosducin is indeed phosphorylated on a serine residue and exists in a phosphorylated form in darkness and that its dephosphorylation occurs in light [29].
  • A nuclear preparation was obtained from the homogenate by sucrose gradient centrifugation, its purity was determined with a nuclear stain, and the presence and phosphorylation of phosducin was investigated as above [30].

Physical interactions of PDC


Enzymatic interactions of PDC

  • These results, together with the finding that GRK2 may phosphorylate synuclein and phosducin in their acidic domains, indicate that some proteins with very acidic regions but without basic activation domains could serve as substrates for GRK2 [33].

Regulatory relationships of PDC


Other interactions of PDC


Analytical, diagnostic and therapeutic context of PDC


  1. Altered maturation of circulating dendritic cells in primary progressive MS patients. López, C., Comabella, M., Al-zayat, H., Tintoré, M., Montalban, X. J. Neuroimmunol. (2006) [Pubmed]
  2. Novel environmental toxins: Steryl glycosides as a potential etiological factor for age-related neurodegenerative diseases. Ly, P.T., Singh, S., Shaw, C.A. J. Neurosci. Res. (2007) [Pubmed]
  3. Commentary on: return of the cycad hypothesis - does the amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC) of Guam have new implications for global health? Cox, P.A., Banack, S., Murch, S., Sacks, O. Neuropathol. Appl. Neurobiol. (2006) [Pubmed]
  4. The paroxysmal dyskinesias. Bhatia, K.P. J. Neurol. (1999) [Pubmed]
  5. Pigmentary retinopathy of ALS/PDC in Kii. Kokubo, Y., Ito, K., Fukunaga, T., Matsubara, H., Kuzuhara, S. Ophthalmology (2006) [Pubmed]
  6. Two sites in the MAPT region confer genetic risk for Guam ALS/PDC and dementia. Sundar, P.D., Yu, C.E., Sieh, W., Steinbart, E., Garruto, R.M., Oyanagi, K., Craig, U.K., Bird, T.D., Wijsman, E.M., Galasko, D.R., Schellenberg, G.D. Hum. Mol. Genet. (2007) [Pubmed]
  7. Tau and alpha-synuclein pathology in amygdala of Parkinsonism-dementia complex patients of Guam. Forman, M.S., Schmidt, M.L., Kasturi, S., Perl, D.P., Lee, V.M., Trojanowski, J.Q. Am. J. Pathol. (2002) [Pubmed]
  8. Effects of Tai Chi exercise on physical and mental health of college students. Wang, Y.T., Taylor, L., Pearl, M., Chang, L.S. Am. J. Chin. Med. (2004) [Pubmed]
  9. The X-Linked Mental Retardation Gene SMCX/JARID1C Defines a Family of Histone H3 Lysine 4 Demethylases. Iwase, S., Lan, F., Bayliss, P., de la Torre-Ubieta, L., Huarte, M., Qi, H.H., Whetstine, J.R., Bonni, A., Roberts, T.M., Shi, Y. Cell (2007) [Pubmed]
  10. Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma. Zhang, Y., Leaves, N.I., Anderson, G.G., Ponting, C.P., Broxholme, J., Holt, R., Edser, P., Bhattacharyya, S., Dunham, A., Adcock, I.M., Pulleyn, L., Barnes, P.J., Harper, J.I., Abecasis, G., Cardon, L., White, M., Burton, J., Matthews, L., Mott, R., Ross, M., Cox, R., Moffatt, M.F., Cookson, W.O. Nat. Genet. (2003) [Pubmed]
  11. MHC class I ubiquitination by a viral PHD/LAP finger protein. Boname, J.M., Stevenson, P.G. Immunity (2001) [Pubmed]
  12. Nuclear PtdIns5P as a transducer of stress signaling: an in vivo role for PIP4Kbeta. Jones, D.R., Bultsma, Y., Keune, W.J., Halstead, J.R., Elouarrat, D., Mohammed, S., Heck, A.J., D'Santos, C.S., Divecha, N. Mol. Cell (2006) [Pubmed]
  13. Heterogeneity of autoreactive T cell clones specific for the E2 component of the pyruvate dehydrogenase complex in primary biliary cirrhosis. Van de Water, J., Ansari, A., Prindiville, T., Coppel, R.L., Ricalton, N., Kotzin, B.L., Liu, S., Roche, T.E., Krams, S.M., Munoz, S., Gershwin, M.E. J. Exp. Med. (1995) [Pubmed]
  14. Human monoclonal antibodies from a patient with primary biliary cirrhosis that recognize two distinct autoepitopes in the E2 component of the pyruvate dehydrogenase complex. Matsui, M., Nakamura, M., Ishibashi, H., Koike, K., Kudo, J., Niho, Y. Hepatology (1993) [Pubmed]
  15. Glutamate leakage from a compartmentalized intracellular metabolic pool and activation of the lipoxygenase pathway mediate oxidative astrocyte death by reversed glutamate transport. Re, D.B., Nafia, I., Melon, C., Shimamoto, K., Goff, L.K., Had-Aissouni, L. Glia (2006) [Pubmed]
  16. Isolation of various forms of sterol beta-D-glucoside from the seed of Cycas circinalis: neurotoxicity and implications for ALS-parkinsonism dementia complex. Khabazian, I., Bains, J.S., Williams, D.E., Cheung, J., Wilson, J.M., Pasqualotto, B.A., Pelech, S.L., Andersen, R.J., Wang, Y.T., Liu, L., Nagai, A., Kim, S.U., Craig, U.K., Shaw, C.A. J. Neurochem. (2002) [Pubmed]
  17. Damage and repair of nerve cell DNA in toxic stress. Kisby, G.E., Kabel, H., Hugon, J., Spencer, P. Drug Metab. Rev. (1999) [Pubmed]
  18. Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor. Appelhoff, R.J., Tian, Y.M., Raval, R.R., Turley, H., Harris, A.L., Pugh, C.W., Ratcliffe, P.J., Gleadle, J.M. J. Biol. Chem. (2004) [Pubmed]
  19. Phosphorylation of phosducin and phosducin-like protein by G protein-coupled receptor kinase 2. Ruiz-Gómez, A., Humrich, J., Murga, C., Quitterer, U., Lohse, M.J., Mayor, F. J. Biol. Chem. (2000) [Pubmed]
  20. PhLPs and PhLOPs in the phosducin family of G beta gamma binding proteins. Craft, C.M., Xu, J., Slepak, V.Z., Zhan-Poe, X., Zhu, X., Brown, B., Lolley, R.N. Biochemistry (1998) [Pubmed]
  21. Regulation of exocytosis in chromaffin cells by phosducin-like protein, a protein interacting with G protein betagamma subunits. Gensse, M., Vitale, N., Chasserot-Golaz, S., Bader, M.F. FEBS Lett. (2000) [Pubmed]
  22. Phosducin, potential role in modulation of olfactory signaling. Boekhoff, I., Touhara, K., Danner, S., Inglese, J., Lohse, M.J., Breer, H., Lefkowitz, R.J. J. Biol. Chem. (1997) [Pubmed]
  23. Determination of the G beta gamma-binding domain of phosducin. A regulatable modulator of G beta gamma signaling. Hawes, B.E., Touhara, K., Kurose, H., Lefkowitz, R.J., Inglese, J. J. Biol. Chem. (1994) [Pubmed]
  24. Assignment of the phosducin (PDC) gene to human chromosome 1q25-1q32.1 by somatic cell hybridization and in situ hybridization. Sparkes, R.S., Lee, R.H., Shinohara, T., Craft, C.M., Kojis, T., Klisak, I., Heinzmann, C., Bateman, J.B. Genomics (1993) [Pubmed]
  25. Isolation and analysis of the human MEKA gene encoding a retina-specific protein. Watanabe, Y., Kawasaki, K., Miki, N., Kuo, C.H. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  26. Cooperative induction of a tolerogenic dendritic cell phenotype by cytokines secreted by pancreatic carcinoma cells. Bellone, G., Carbone, A., Smirne, C., Scirelli, T., Buffolino, A., Novarino, A., Stacchini, A., Bertetto, O., Palestro, G., Sorio, C., Scarpa, A., Emanuelli, G., Rodeck, U. J. Immunol. (2006) [Pubmed]
  27. Phosducin and phosducin-like protein attenuate G-protein-coupled receptor-mediated inhibition of voltage-gated calcium channels in rat sympathetic neurons. Partridge, J.G., Puhl, H.L., Ikeda, S.R. Mol. Pharmacol. (2006) [Pubmed]
  28. Proteomic Analysis of the Genotoxicant Methylazoxymethanol (MAM)-Induced Changes in the Developing Cerebellum. Kisby, G.E., Standley, M., Park, T., Olivas, A., Fei, S., Jacob, T., Reddy, A., Lu, X., Pattee, P., Nagalla, S.R. J. Proteome Res. (2006) [Pubmed]
  29. Identification of possible phosducins in the ciliate Blepharisma japonicum. Fabczak, H., Sobierajska, K., Fabczak, S. Protist (2004) [Pubmed]
  30. Presence of phosducin in the nuclei of bovine retinal cells. Margulis, A., Dang, L., Pulukuri, S., Lee, R., Sitaramayya, A. Mol. Vis. (2002) [Pubmed]
  31. Immunohistochemical study of the hippocampus in parkinsonism-dementia complex on Guam. Ito, H., Goto, S., Hirano, A., Yen, S.H. Journal of geriatric psychiatry and neurology. (1991) [Pubmed]
  32. Interactions of phosducin with the subunits of G-proteins. Binding to the alpha as well as the betagamma subunits. Bauer, P.H., Blüml, K., Schröder, S., Hegler, J., Dees, C., Lohse, M.J. J. Biol. Chem. (1998) [Pubmed]
  33. Identification of sites of phosphorylation by G-protein-coupled receptor kinase 2 in beta-tubulin. Yoshida, N., Haga, K., Haga, T. Eur. J. Biochem. (2003) [Pubmed]
  34. Phosducin inhibits receptor phosphorylation by the beta-adrenergic receptor kinase in a PKA-regulated manner. Hekman, M., Bauer, P.H., Söhlemann, P., Lohse, M.J. FEBS Lett. (1994) [Pubmed]
  35. The gene for human phosducin (PDC), a soluble protein that binds G-protein beta gamma dimers, maps to 1q25-q31.1. Ding, C., Li, X., Griffin, C.A., Jabs, E.W., Hawkins, A.L., Levine, M.A. Genomics (1993) [Pubmed]
  36. Mutation screening of the phosducin gene PDC in patients with retinitis pigmentosa and allied diseases. Nishiguchi, K.M., Berson, E.L., Dryja, T.P. Mol. Vis. (2004) [Pubmed]
  37. Differential dysfunction in dendritic cell subsets during chronic HCV infection. Averill, L., Lee, W.M., Karandikar, N.J. Clin. Immunol. (2007) [Pubmed]
  38. Molecular cloning and characterization of the human phosducin-like protein (hPhLP) promoter. Lazarov, M.E., Martin, M.M., Willardson, B.M., Elton, T.S. Biochim. Biophys. Acta (2000) [Pubmed]
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