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Gene Review

PDCD6  -  programmed cell death 6

Homo sapiens

Synonyms: ALG-2, ALG2, Apoptosis-linked gene 2 protein, PEF1B, Programmed cell death protein 6
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Disease relevance of PDCD6


Psychiatry related information on PDCD6


High impact information on PDCD6


Biological context of PDCD6


Anatomical context of PDCD6


Associations of PDCD6 with chemical compounds

  • Surprisingly, peflin dissociated from ALG-2 in the presence of Ca(2+) [4].
  • The mammalian adaptor protein Alix [ALG-2 (apoptosis-linked-gene-2 product)-interacting protein X] belongs to a conserved family of proteins that have in common an N-terminal Bro1 domain and a C-terminal PRD (proline-rich domain), both of which mediate partner protein interactions [11].
  • In this work, we show that in the ALG-2-depleted clones the ICE/Ced-3 proteases are normally activated upon TCR, Fas, and dexamethasone stimulation, as determined by cleavage of the endogenous substrate poly(ADP-ribose) polymerase and of a fluorogenic substrate [12].
  • In contrast, treatment of cells with the membrane-permeant Ca(2+) chelator BAPTA-AM led to a dispersion of ALG-2 throughout the cells and to a significant loss of Sec31A in the perinuclear region [13].
  • Biochemical and immunofluorescent microscopic analyses showed that ALG-2 was enriched at the Sec31A-localizing membrane compartments upon stimulation with the Ca(2+) ionophore A23187 [13].

Physical interactions of PDCD6


Enzymatic interactions of PDCD6


Other interactions of PDCD6

  • In the course of identifying new substrates of Raf-1, we found that the Raf-1 kinase domain interacted with apoptosis-linked gene-2 (ALG-2) in yeast two-hybrid system [7].
  • This observation supports the hypothesis, formulated on the basis of the structure of a homologous protein ALG-2 which shows significant differences in the orientation of EF4 and EF5 compared with grancalcin, that calcium is a necessary factor but not sufficient alone for inducing a significant conformational change in PEF proteins [17].
  • The role of Ca(2+) as one of the key regulators of the cell is discussed with respect to two recently discovered proteins, ALG-2 and AIP, of which the former is a Ca(2+)-binding protein, and the latter is substrate to various kinases [15].
  • Serial gene analysis of expression revealed the downregulation of voltage-dependent anion channels 1 and 2 genes and the upregulation of the cytochrome c oxidase and calcium binding protein genes (calpactin, calgizzarin and programmed cell death 6) [18].
  • It was 85% at 1 year, 70% at 3 years, and 62% at 5 years in the ALG 2 regimen group and 87% at 1 year and 67% at 3 years in the ALG 3 regimen group [19].

Analytical, diagnostic and therapeutic context of PDCD6

  • This was confirmed by Western blotting of the immunoprecipitates of epitope-tagged peflin or ALG-2 whose cDNA expression constructs were transfected to human embryonic kidney (HEK) 293 cells [4].
  • The specificity of the antibody was shown by preabsorbtion experiments and on ALG-2-deficient cells using Western blot analysis and immunohistochemistry [1].
  • Crystallization and preliminary crystallographic studies of an apoptosis-linked calcium-binding protein ALG-2 [20].
  • Intracellular localization of the penta-EF-hand Ca(2+)-binding protein ALG-2 in HeLa cells was investigated by immunofluorescent confocal microscopy using a polyclonal antibody [13].


  1. Up-regulation of ALG-2 in hepatomas and lung cancer tissue. la Cour, J.M., Mollerup, J., Winding, P., Tarabykina, S., Sehested, M., Berchtold, M.W. Am. J. Pathol. (2003) [Pubmed]
  2. Interfering with apoptosis: Ca(2+)-binding protein ALG-2 and Alzheimer's disease gene ALG-3. Vito, P., Lacanà, E., D'Adamio, L. Science (1996) [Pubmed]
  3. The Ca2+-binding Protein ALG-2 Is Recruited to Endoplasmic Reticulum Exit Sites by Sec31A and Stabilizes the Localization of Sec31A. Yamasaki, A., Tani, K., Yamamoto, A., Kitamura, N., Komada, M. Mol. Biol. Cell (2006) [Pubmed]
  4. Peflin and ALG-2, members of the penta-EF-hand protein family, form a heterodimer that dissociates in a Ca2+-dependent manner. Kitaura, Y., Matsumoto, S., Satoh, H., Hitomi, K., Maki, M. J. Biol. Chem. (2001) [Pubmed]
  5. Two forms of the apoptosis-linked protein ALG-2 with different Ca(2+) affinities and target recognition. Tarabykina, S., Møller, A.L., Durussel, I., Cox, J., Berchtold, M.W. J. Biol. Chem. (2000) [Pubmed]
  6. Programmed cell death 6 (PDCD6) protein interacts with death-associated protein kinase 1 (DAPk1): additive effect on apoptosis via caspase-3 dependent pathway. Lee, J.H., Rho, S.B., Chun, T. Biotechnol. Lett. (2005) [Pubmed]
  7. Apoptosis-linked gene-2 connects the Raf-1 and ASK1 signalings. Chen, C., Sytkowski, A.J. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  8. ALG-2: a Ca2+ -binding modulator protein involved in cell proliferation and in cell death. Krebs, J., Saremaslani, P., Caduff, R. Biochim. Biophys. Acta (2002) [Pubmed]
  9. Cloning of AIP1, a novel protein that associates with the apoptosis-linked gene ALG-2 in a Ca2+-dependent reaction. Vito, P., Pellegrini, L., Guiet, C., D'Adamio, L. J. Biol. Chem. (1999) [Pubmed]
  10. The glioma-associated protein SETA interacts with AIP1/Alix and ALG-2 and modulates apoptosis in astrocytes. Chen, B., Borinstein, S.C., Gillis, J., Sykes, V.W., Bogler, O. J. Biol. Chem. (2000) [Pubmed]
  11. Phosphorylation of the proline-rich domain of Xp95 modulates Xp95 interaction with partner proteins. Dejournett, R.E., Kobayashi, R., Pan, S., Wu, C., Etkin, L.D., Clark, R.B., B??gler, O., Kuang, J. Biochem. J. (2007) [Pubmed]
  12. Dissociation of apoptosis and activation of IL-1beta-converting enzyme/Ced-3 proteases by ALG-2 and the truncated Alzheimer's gene ALG-3. Lacanà, E., Ganjei, J.K., Vito, P., D'Adamio, L. J. Immunol. (1997) [Pubmed]
  13. ALG-2 directly binds Sec31A and localizes at endoplasmic reticulum exit sites in a Ca(2+)-dependent manner. Shibata, H., Suzuki, H., Yoshida, H., Maki, M. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  14. Interaction of ALG-2 with ASK1 influences ASK1 localization and subsequent JNK activation. Hwang, I.S., Jung, Y.S., Kim, E. FEBS Lett. (2002) [Pubmed]
  15. The ALG-2/AIP-complex, a modulator at the interface between cell proliferation and cell death? A hypothesis. Krebs, J., Klemenz, R. Biochim. Biophys. Acta (2000) [Pubmed]
  16. Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide complex: Ca2+/EF3-driven arginine switch mechanism. Suzuki, H., Kawasaki, M., Inuzuka, T., Okumura, M., Kakiuchi, T., Shibata, H., Wakatsuki, S., Maki, M. Structure (2008) [Pubmed]
  17. Structure of Ca(2+)-loaded human grancalcin. Jia, J., Borregaard, N., Lollike, K., Cygler, M. Acta Crystallogr. D Biol. Crystallogr. (2001) [Pubmed]
  18. Transcriptome analysis and gene expression profiles of early apoptosis-related genes in Streptococcus pyogenes-infected epithelial cells. Nakagawa, I., Nakata, M., Kawabata, S., Hamada, S. Cell. Microbiol. (2004) [Pubmed]
  19. Immunosuppressive treatment of primary cadaveric renal transplant patients receiving kidneys from non-heart beating donors. Ohshima, S., Fujita, T., Ono, Y., Kinukawa, T., Katoh, N., Matsuura, O. Artificial organs. (1996) [Pubmed]
  20. Crystallization and preliminary crystallographic studies of an apoptosis-linked calcium-binding protein ALG-2. Wu, F., Zhang, M., Gong, W. Acta Crystallogr. D Biol. Crystallogr. (2001) [Pubmed]
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