Gene Symbol: Pdcd6
Description: programmed cell death 6
Alias: ALG-2, programmed cell death protein 6, apoptosis-linked gene 2 protein homolog
Species: rat
Products:     Pdcd6

Top Publications

  1. Vito P, Lacana E, D ADAMIO L. Interfering with apoptosis: Ca(2+)-binding protein ALG-2 and Alzheimer's disease gene ALG-3. Science. 1996;271:521-5 pubmed
    ..These findings suggest that ALG-2 may mediate Ca(2+)-regulated signals along the death pathway and that cell death may play a role in Alzheimer's disease. ..
  2. Shibata H, Suzuki H, Yoshida H, Maki M. ALG-2 directly binds Sec31A and localizes at endoplasmic reticulum exit sites in a Ca2+-dependent manner. Biochem Biophys Res Commun. 2007;353:756-63 pubmed
    ..These findings establish Sec31A as a novel target for ALG-2 and provide a framework for studies on the roles of ALG-2 in ER-Golgi transport. ..
  3. la Cour J, Mollerup J, Berchtold M. ALG-2 oscillates in subcellular localization, unitemporally with calcium oscillations. Biochem Biophys Res Commun. 2007;353:1063-7 pubmed
  4. Rao R, Poksay K, Castro Obregon S, Schilling B, Row R, Del Rio G, et al. Molecular components of a cell death pathway activated by endoplasmic reticulum stress. J Biol Chem. 2004;279:177-87 pubmed
    ..Our data identify two molecules, valosin-containing protein and apoptosis-linked gene-2 (ALG-2), that appear to play a role in mediating ER stress-induced cell death. ..
  5. Yamasaki A, Tani K, Yamamoto A, Kitamura N, Komada M. The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum exit sites by Sec31A and stabilizes the localization of Sec31A. Mol Biol Cell. 2006;17:4876-87 pubmed
    ..We conclude that ALG-2 is recruited to ER exit sites via Ca(2+)-dependent interaction with Sec31A and in turn stabilizes the localization of Sec31A at these sites. ..
  6. Shibata H, Suzuki H, Kakiuchi T, Inuzuka T, Yoshida H, Mizuno T, et al. Identification of Alix-type and Non-Alix-type ALG-2-binding sites in human phospholipid scramblase 3: differential binding to an alternatively spliced isoform and amino acid-substituted mutants. J Biol Chem. 2008;283:9623-32 pubmed publisher
    ..GST-pulldown assays using single amino acid-substituted ALG-2 mutants revealed differences in binding specificities between the two groups, suggesting structural flexibility in ALG-2-ligand complex formation. ..
  7. Suzuki H, Kawasaki M, Inuzuka T, Okumura M, Kakiuchi T, Shibata H, et al. Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide complex: Ca2+/EF3-driven arginine switch mechanism. Structure. 2008;16:1562-73 pubmed publisher
    ..Based on these results, together with the results of in vitro binding assay with mutant ALG-2 and Alix proteins, we propose a Ca(2+)/EF3-driven arginine switch mechanism for ALG-2 binding to Alix. ..
  8. Missotten M, Nichols A, Rieger K, Sadoul R. Alix, a novel mouse protein undergoing calcium-dependent interaction with the apoptosis-linked-gene 2 (ALG-2) protein. Cell Death Differ. 1999;6:124-9 pubmed
    ..elegans protein (YNK-1) and to proteins of A. nidulans (PalA) and S. cerevisiae (BRO1). Alix is a potential regulator or downstream effector of ALG-2 action. ..
  9. Okumura M, Katsuyama A, Shibata H, Maki M. VPS37 isoforms differentially modulate the ternary complex formation of ALIX, ALG-2, and ESCRT-I. Biosci Biotechnol Biochem. 2013;77:1715-21 pubmed
    ..The results of in vitro binding assays using purified recombinant proteins indicated that ALG-2 functions as a Ca²?-dependent adaptor protein that bridges ALIX and ESCRT-I to form a ternary complex, ESCRT-I/ALIX/ALG-2. ..

More Information


  1. Rho S, Song Y, Lim M, Lee S, Kim B, Park S. Programmed cell death 6 (PDCD6) inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of VEGFR-2. Cell Signal. 2012;24:131-9 pubmed publisher
    Programmed cell death 6 (PDCD6) was originally found as a pro-apoptotic protein, but its molecular mechanism is not well understood...
  2. Okumura M, Ichioka F, Kobayashi R, Suzuki H, Yoshida H, Shibata H, et al. Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101. Biochem Biophys Res Commun. 2009;386:237-41 pubmed publisher
    ..Based on the X-ray crystal structure model showing the presence of one ligand-binding site in each molecule of an ALG-2 dimer, we propose that Ca2+-loaded ALG-2 bridges Alix and TSG101 as an adaptor protein. ..
  3. Janowicz A, Michalak M, Krebs J. Stress induced subcellular distribution of ALG-2, RBM22 and hSlu7. Biochim Biophys Acta. 2011;1813:1045-9 pubmed publisher
    ..The article is part of a Special Issue entitled: 11th European Symposium on Calcium. ..
  4. Kitaura Y, Satoh H, Takahashi H, Shibata H, Maki M. Both ALG-2 and peflin, penta-EF-hand (PEF) proteins, are stabilized by dimerization through their fifth EF-hand regions. Arch Biochem Biophys. 2002;399:12-8 pubmed
    ..On the other hand, stable expression of exogenous peflin decreased the amount of endogenous peflin. The amount of peflin that can dimerize with ALG-2 seems to be restricted in mammalian cells. ..
  5. Lee J, Rho S, Chun T. Programmed cell death 6 (PDCD6) protein interacts with death-associated protein kinase 1 (DAPk1): additive effect on apoptosis via caspase-3 dependent pathway. Biotechnol Lett. 2005;27:1011-5 pubmed
    Programmed cell death 6 (PDCD6) protein is a 22 kDa EF-hand type Ca(2+)-binding protein involved in apoptosis...
  6. Takahashi T, Kojima K, Zhang W, Sasaki K, Ito M, Suzuki H, et al. Structural analysis of the complex between penta-EF-hand ALG-2 protein and Sec31A peptide reveals a novel target recognition mechanism of ALG-2. Int J Mol Sci. 2015;16:3677-99 pubmed publisher
    ..We conclude that ALG-2 recognizes two types of motifs at different hydrophobic surfaces. Furthermore, based on the results of serial mutational analysis of the ALG-2-binding sites in Sec31A, the type 2 motif was newly defined. ..
  7. McGourty C, Akopian D, Walsh C, Gorur A, Werner A, Schekman R, et al. Regulation of the CUL3 Ubiquitin Ligase by a Calcium-Dependent Co-adaptor. Cell. 2016;167:525-538.e14 pubmed publisher
    ..Our work, therefore, identifies both calcium and CUL3 co-adaptors as important regulators of ubiquitylation events that control human development. ..
  8. Ma J, Zhang X, Feng Y, Zhang H, Wang X, Zheng Y, et al. Structural and Functional Study of Apoptosis-linked Gene-2·Heme-binding Protein 2 Interactions in HIV-1 Production. J Biol Chem. 2016;291:26670-26685 pubmed publisher
    ..ALG-2, also known as PDCD6, interacts with both ALIX and TSG101 and bridges ESCRT-III and ESCRT-I...
  9. Kanadome T, Shibata H, Kuwata K, Takahara T, Maki M. The calcium-binding protein ALG-2 promotes endoplasmic reticulum exit site localization and polymerization of Trk-fused gene (TFG) protein. FEBS J. 2017;284:56-76 pubmed publisher
    Apoptosis-linked gene 2 (ALG-2), which is a gene product of PDCD6, is a 22-kDa Ca2+ -binding protein. Accumulating evidence points to a role for ALG-2 as a Ca2+ -responsive adaptor protein...
  10. Tanner J, Frey B, Pemberton T, Henzl M. EF5 Is the High-Affinity Mg(2+) Site in ALG-2. Biochemistry. 2016;55:5128-41 pubmed publisher
    ..The results of a calorimetry-based analysis indicate that their Mg(2+) binding constants are 2 orders of magnitude lower than that determined for EF5. ..