Gene Symbol: ALG 2
Description: programmed cell death 6
Alias: ALG-2, ALG2, PEF1B, programmed cell death protein 6, apoptosis-linked gene 2 protein, apoptosis-linked gene 2 protein homolog
Species: human
Products:     ALG 2

Top Publications

  1. Yamada Y, Arao T, Gotoda T, Taniguchi H, Oda I, Shirao K, et al. Identification of prognostic biomarkers in gastric cancer using endoscopic biopsy samples. Cancer Sci. 2008;99:2193-9 pubmed publisher
    ..Our PCR-based single gene prediction strategy successfully predicted the overall survival and may lead to a better understanding of this disease subgroup. ..
  2. Suzuki K, Dashzeveg N, Lu Z, Taira N, Miki Y, Yoshida K. Programmed cell death 6, a novel p53-responsive gene, targets to the nucleus in the apoptotic response to DNA damage. Cancer Sci. 2012;103:1788-94 pubmed publisher
    ..Therefore, we conclude that a novel p53-responsive gene PDCD6 is accumulated in the nucleus and induces apoptosis in response to DNA damage. ..
  3. 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. ..
  4. Vito P, Pellegrini L, Guiet C, D ADAMIO L. Cloning of AIP1, a novel protein that associates with the apoptosis-linked gene ALG-2 in a Ca2+-dependent reaction. J Biol Chem. 1999;274:1533-40 pubmed
  5. Jung Y, Kim K, Kim K, Lim J, Kim J, Kim E. Apoptosis-linked gene 2 binds to the death domain of Fas and dissociates from Fas during Fas-mediated apoptosis in Jurkat cells. Biochem Biophys Res Commun. 2001;288:420-6 pubmed
  6. Satoh H, Nakano Y, Shibata H, Maki M. The penta-EF-hand domain of ALG-2 interacts with amino-terminal domains of both annexin VII and annexin XI in a Ca2+-dependent manner. Biochim Biophys Acta. 2002;1600:61-7 pubmed
    ..Two binding sites were predicted in both Anx7N and Anx11N, and the dissociation constants (K(d)) were estimated to be approximately 40-60 nM for the high-affinity site and 500-700 nM for the low-affinity site. ..
  7. Katoh K, Suzuki H, Terasawa Y, Mizuno T, Yasuda J, Shibata H, et al. The penta-EF-hand protein ALG-2 interacts directly with the ESCRT-I component TSG101, and Ca2+-dependently co-localizes to aberrant endosomes with dominant-negative AAA ATPase SKD1/Vps4B. Biochem J. 2005;391:677-85 pubmed
    ..Our findings suggest that ALG-2 may function as a Ca2+-dependent accessory protein of the endosomal sorting machinery by interacting directly with TSG101 as well as with Alix. ..
  8. 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. ..
  9. 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. ..

More Information

Publications105 found, 100 shown here

  1. 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. ..
  2. la Cour J, Mollerup J, Winding P, Tarabykina S, Sehested M, Berchtold M. Up-regulation of ALG-2 in hepatomas and lung cancer tissue. Am J Pathol. 2003;163:81-9 pubmed
    ..Our results lead to the conclusion that ALG-2 beside its known proapoptotic functions may be a player in survival pathways. ..
  3. Shibata H, Yamada K, Mizuno T, Yorikawa C, Takahashi H, Satoh H, et al. The penta-EF-hand protein ALG-2 interacts with a region containing PxY repeats in Alix/AIP1, which is required for the subcellular punctate distribution of the amino-terminal truncation form of Alix/AIP1. J Biochem. 2004;135:117-28 pubmed
    ..These results indicate the requirement of ABS in Alix for the efficient accumulation of AlixCT and raise the possibility that ALG-2 participates in membrane trafficking through a Ca(2+)-dependent interaction with Alix. ..
  4. Chen C, Sytkowski A. Apoptosis-linked gene-2 connects the Raf-1 and ASK1 signalings. Biochem Biophys Res Commun. 2005;333:51-7 pubmed
    ..Since ALG-2 associates with ASK1, and both ASK1 and ALG-2 are involved in apoptosis, our observations indicate that Raf-1 may mediate its anti-apoptotic function by interrupting ASK1-dependent phosphorylation of ALG-2. ..
  5. 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. ..
  6. 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
  7. 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. ..
  8. 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
    ..We found binding PDCD6 to VEGFR-2, a key player in the PI3K/mTOR/P70S6K signaling pathway. Taken together, these data suggest that PDCD6 plays a significant role in modulating cellular angiogenesis. ..
  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. ..
  10. Sasaki Osugi K, Imoto C, Takahara T, Shibata H, Maki M. Nuclear ALG-2 protein interacts with Ca2+ homeostasis endoplasmic reticulum protein (CHERP) Ca2+-dependently and participates in regulation of alternative splicing of inositol trisphosphate receptor type 1 (IP3R1) pre-mRNA. J Biol Chem. 2013;288:33361-75 pubmed publisher
    ..These results indicate that CHERP and ALG-2 participate in regulation of alternative splicing of IP3R1 pre-mRNA and provide new insights into post-transcriptional regulation of splicing variants in Ca(2+) signaling pathways. ..
  11. Działo E, Rudnik M, Koning R, Czepiel M, Tkacz K, Baj Krzyworzeka M, et al. WNT3a and WNT5a Transported by Exosomes Activate WNT Signaling Pathways in Human Cardiac Fibroblasts. Int J Mol Sci. 2019;20: pubmed publisher
  12. Marques J, Del Valle T, Ghizzi L, Zilio E, Gheller L, Nunes A, et al. Increasing dietary levels of docosahexaenoic acid-rich microalgae: Ruminal fermentation, animal performance, and milk fatty acid profile of mid-lactating dairy cows. J Dairy Sci. 2019;: pubmed publisher
    ..Estimated intermediate doses (1.22 to 2.90 g/kg of DM) of DHA-rich ALG may be beneficial to milk, fat-corrected milk, and energy-corrected milk yields, and is recommended for dairy cows. ..
  13. Cho H, Mook Jung I. O-GlcNAcylation regulates endoplasmic reticulum exit sites through Sec31A modification in conventional secretory pathway. FASEB J. 2018;32:4641-4657 pubmed publisher
    ..Cho, H. J., Mook-Jung, I. O-GlcNAcylation regulates endoplasmic reticulum exit sites through Sec31A modification in conventional secretory pathway. ..
  14. Chebib N, Kalberer N, Srinivasan M, Maniewicz S, Perneger T, Muller F. Edentulous jaw impression techniques: An in vivo comparison of trueness. J Prosthet Dent. 2019;121:623-630 pubmed publisher
    ..75). Edentulous impressions made with PVS, PVSM, and TRI had similar deviations and may yield clinically acceptable results. Irreversible hydrocolloids are contraindicated for definitive impression making in completely edentulous jaws. ..
  15. Das D, Pham H, Lee S, Noh I. Fabrication of alginate-based stimuli-responsive, non-cytotoxic, terpolymric semi-IPN hydrogel as a carrier for controlled release of bovine albumin serum and 5-amino salicylic acid. Mater Sci Eng C Mater Biol Appl. 2019;98:42-53 pubmed publisher
  16. Wang N, Zhan J, Guo C, Li C, Shen N, Gu X, et al. Molecular Characterisation and Functions of Fis1 and PDCD6 Genes from Echinococcus granulosus. Int J Mol Sci. 2018;19: pubmed publisher
    ..Herein, we cloned, expressed, and characterised mitochondrial fission protein 1 (Eg-Fis1) and programmed cell death protein 6 (Eg-PDCD6) from E. granulosus, and explored their functions related to infertile cysts...
  17. Maki M, Takahara T, Shibata H. Multifaceted Roles of ALG-2 in Ca(2+)-Regulated Membrane Trafficking. Int J Mol Sci. 2016;17: pubmed publisher
    ..Binding of ALG-2 to targets may induce conformational change of the proteins. The ALG-2 dimer may also function as a Ca(2+)-dependent adaptor to bridge different partners and connect the subnetwork of interacting proteins. ..
  18. Chaturbhuj D, Patil A, Gangakhedkar R. PYRE insertion within HIV-1 subtype C p6-Gag functions as an ALIX-dependent late domain. Sci Rep. 2018;8:8917 pubmed publisher
    ..In summary, our data reveals the functional role of PYRE insertion towards the cooperative mechanism of ALIX/Nedd4-1 in virus release in the absence of PTAP/Tsg101 pathway. ..
  19. Zhang W, Matsuo R, Takahara T, Shibata H, Maki M. High Sensitive Quantitative Binding Assays Using a Nanoluciferase-Fused Probe for Analysis of ALG-2-Interacting Proteins. Methods Mol Biol. 2019;1929:501-516 pubmed publisher
    ..Application of nanoluciferase (Nluc)-fused ALG-2 enables a rapid quantitative evaluation of Ca2+-dependent interactions of target proteins with ALG-2 in vitro binding assays. ..
  20. Inuzuka T, Suzuki H, Kawasaki M, Shibata H, Wakatsuki S, Maki M. Molecular basis for defect in Alix-binding by alternatively spliced isoform of ALG-2 (ALG-2DeltaGF122) and structural roles of F122 in target recognition. BMC Struct Biol. 2010;10:25 pubmed publisher
    ..Moreover, a residue at the position of F122 contributes to target specificity and a smaller side chain is preferable for Alix binding but not favored to bind annexin A11. ..
  21. Shibata H. Adaptor functions of the Ca2+-binding protein ALG-2 in protein transport from the endoplasmic reticulum. Biosci Biotechnol Biochem. 2019;83:20-32 pubmed publisher
  22. Thepparit C, Khongwichit S, Ketsuwan K, Libsittikul S, Auewarakul P, Smith D. Dengue virus requires apoptosis linked gene-2-interacting protein X (ALIX) for viral propagation. Virus Res. 2019;261:65-71 pubmed publisher
    ..These results are consistent with ALIX playing a significant role in the DENV replication cycle either during late infection or at viral egress. ..
  23. Mikasa T, Kugo M, Nishimura S, Taketani S, Ishijima S, Sagami I. Thermodynamic Characterization of the Ca2+-Dependent Interaction Between SOUL and ALG-2. Int J Mol Sci. 2018;19: pubmed publisher
    ..These results provide a better understanding of the target recognition mechanism and conformational change of SOUL in the interaction with ALG-2. ..
  24. Bentley M, Nycz D, Joglekar A, Fertschai I, Malli R, Graier W, et al. Vesicular calcium regulates coat retention, fusogenicity, and size of pre-Golgi intermediates. Mol Biol Cell. 2010;21:1033-46 pubmed publisher
    ..We propose that in cells, these Ca(2+)-dependent mechanisms temporally regulate COPII vesicle interactions, VTC biogenesis, cargo sorting, and VTC maturation. ..
  25. Liu X. Up-regulation of miR-20a by HPV16 E6 exerts growth-promoting effects by targeting PDCD6 in cervical carcinoma cells. Biomed Pharmacother. 2018;102:996-1002 pubmed publisher
    ..Up-regulation of miR-20a by HPV16 E6 exerted growth-promoting effects by targeting PDCD6 in cervical carcinoma cells. This study demonstrated miR-20a might be a potential therapeutic target in HPV16 E6 infection type of cervical cancer. ..
  26. Sammar M, Dragovic R, Meiri H, Vatish M, Sharabi Nov A, Sargent I, et al. Reduced placental protein 13 (PP13) in placental derived syncytiotrophoblast extracellular vesicles in preeclampsia - A novel tool to study the impaired cargo transmission of the placenta to the maternal organs. Placenta. 2018;66:17-25 pubmed publisher
    ..PP13 is located in and on all types of STB-EVs. Circulating PP13 may therefore be either soluble or associated with extracellular vesicles with different pathophysiological effects in the maternal circulation. ..
  27. Mercier V, Laporte M, Destaing O, Blot B, Blouin C, Pernet Gallay K, et al. ALG-2 interacting protein-X (Alix) is essential for clathrin-independent endocytosis and signaling. Sci Rep. 2016;6:26986 pubmed publisher
    ..In addition to characterizing a new function for Alix, our results highlight Alix ko cells as a unique tool to unravel the biological consequences of CIE. ..
  28. Kaserer A, Casutt M, Sprengel K, Seifert B, Spahn D, Stein P. Comparison of two different coagulation algorithms on the use of allogenic blood products and coagulation factors in severely injured trauma patients: a retrospective, multicentre, observational study. Scand J Trauma Resusc Emerg Med. 2018;26:4 pubmed publisher
  29. Ma S, Cao B, Zhang H, Luo L, Ren Y, Hu T, et al. The lack of Raf-1 kinase feedback regulation enhances antiapoptosis in cancer cells. Oncogene. 2017;36:2014-2022 pubmed publisher
  30. Wynant N, Santos D, Subramanyam S, Verlinden H, Vanden Broeck J. Drosha, Dicer-1 and Argonaute-1 in the desert locust: phylogenetic analyses, transcript profiling and regulation during phase transition and feeding. J Insect Physiol. 2015;75:20-9 pubmed publisher
  31. Henzl M. Ligation events influence ALG-2 dimerization. Biophys Chem. 2018;239:16-28 pubmed publisher
    ..Paradoxically, however, the detergent markedly destabilizes ALG-2 dimers, particularly in the presence of Ca2+. ..
  32. Malerød L, Le Borgne R, Lie Jensen A, Eikenes Å, Brech A, Liestøl K, et al. Centrosomal ALIX regulates mitotic spindle orientation by modulating astral microtubule dynamics. EMBO J. 2018;37: pubmed publisher
    ..Altogether, our results demonstrate a novel evolutionarily conserved role of ALIX in providing robustness to the orientation of the MS by promoting astral MT formation during asymmetric and symmetric cell division. ..
  33. Scheffer L, Sreetama S, Sharma N, Medikayala S, Brown K, Defour A, et al. Mechanism of Ca²⁺-triggered ESCRT assembly and regulation of cell membrane repair. Nat Commun. 2014;5:5646 pubmed publisher
  34. Cheng X, Zhang X, Yu L, Xu H. Calcium signaling in membrane repair. Semin Cell Dev Biol. 2015;45:24-31 pubmed publisher
    ..In this review, we discuss the mechanisms by which the resealing process is promoted by vesicular Ca(2+) channels and Ca(2+) sensors that accumulate at damage sites. ..
  35. Long H, Zhang F, Xu N, Liu G, Diener D, Rosenbaum J, et al. Comparative Analysis of Ciliary Membranes and Ectosomes. Curr Biol. 2016;26:3327-3335 pubmed publisher
    ..In addition, the prevalence of receptors such as agglutinin and ubiquitinated proteins in ciliary ectosomes suggests that they are involved in cell signaling and turnover of ciliary proteins. ..
  36. Valcz G, Galamb O, Krenács T, Spisák S, Kalmár A, Patai Ã, et al. Exosomes in colorectal carcinoma formation: ALIX under the magnifying glass. Mod Pathol. 2016;29:928-38 pubmed publisher
    ..Surprisingly, the expression of ALIX (ALG 2-interacting protein X), involved in multivesicular body (MVB) and exosome formation, was significantly reduced in ..
  37. Qin J, Li D, Zhou Y, Xie S, Du X, Hao Z, et al. Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton. Oncotarget. 2017;8:2745-2757 pubmed publisher
    ..These findings reveal a critical role for ALG-2 in the pathogenesis of breast cancer and have important implications for its diagnosis and therapy. ..
  38. Laporte M, Chatellard C, Vauchez V, Hemming F, Deloulme J, Vossier F, et al. Alix is required during development for normal growth of the mouse brain. Sci Rep. 2017;7:44767 pubmed publisher
    ..Thus Alix-dependent, clathrin independent endocytosis is essential for controlling brain size. ..
  39. Zhang W, Takahara T, Achiha T, Shibata H, Maki M. Nanoluciferase Reporter Gene System Directed by Tandemly Repeated Pseudo-Palindromic NFAT-Response Elements Facilitates Analysis of Biological Endpoint Effects of Cellular Ca2+ Mobilization. Int J Mol Sci. 2018;19: pubmed publisher
    ..The novel reporter gene system is found to be useful for applications to cell signaling research to monitor biological endpoint effects of cellular Ca2+ mobilization. ..
  40. Kalinowska K, Nagel M, Goodman K, Cuyas L, Anzenberger F, Alkofer A, et al. Arabidopsis ALIX is required for the endosomal localization of the deubiquitinating enzyme AMSH3. Proc Natl Acad Sci U S A. 2015;112:E5543-51 pubmed publisher
    ..Taken together, our data indicate that ALIX could function as an important regulator for AMSH3 function at the late endosomes. ..
  41. Ilari A, Fiorillo A, Poser E, Lalioti V, Sundell G, Ivarsson Y, et al. Structural basis of Sorcin-mediated calcium-dependent signal transduction. Sci Rep. 2015;5:16828 pubmed publisher
    ..This domain inhibits the interaction of sorcin with PDCD6, a protein that carries the Sorcin consensus motif, co-localizes with Sorcin in the perinuclear region of the cell and in the midbody and is involved in the onset of apoptosis. ..
  42. Briffa R, Um I, Faratian D, Zhou Y, Turnbull A, Langdon S, et al. Multi-Scale Genomic, Transcriptomic and Proteomic Analysis of Colorectal Cancer Cell Lines to Identify Novel Biomarkers. PLoS ONE. 2015;10:e0144708 pubmed publisher
    ..Amplification of the putative oncogene TRIB1 has been described for the first time in a cohort of CRC patients. ..
  43. Benmoussa A, Lee C, Laffont B, Savard P, Laugier J, Boilard E, et al. Commercial Dairy Cow Milk microRNAs Resist Digestion under Simulated Gastrointestinal Tract Conditions. J Nutr. 2016;146:2206-2215 pubmed
    ..Our results support the existence of interspecies transfer of microRNAs mediated by milk consumption and challenge our current view of exosomes as the sole carriers of milk-derived microRNAs. ..
  44. Rouka E, Simister P, Janning M, Kumbrink J, Konstantinou T, Muniz J, et al. Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3). J Biol Chem. 2015;290:25275-92 pubmed publisher
    ..In conclusion, we have discovered novel interaction candidates for CD2AP and characterized subtle yet significant differences in the recognition preferences of its three SH3 domains for c-CBL, ALIX, and RIN3. ..
  45. Li S, Li F, Sun Z, Zhang X, Xiang J. Differentially proteomic analysis of the Chinese shrimp at WSSV latent and acute infection stages by iTRAQ approach. Fish Shellfish Immunol. 2016;54:629-38 pubmed publisher
    ..The present study provided a comprehensive view of molecular mechanisms regulating WSSV acute infection at the protein level. ..
  46. Vega Y, Arias S, Paradisi I. Most Martin-Bell syndrome (FMR1-related disorder) Venezuelan patients did not show CGG expansion but instead display genetic heterogeneity. J Hum Genet. 2017;62:235-241 pubmed publisher
    ..One heterozygous duplication in exon 6 of the PDCD6 gene (programmed cell death 6) and a heterozygous deletion in exon 5 of the CHL1 gene (cell adhesion molecule L1), respectively, were found in two independent patients. ..
  47. Prudent M, Crettaz D, Delobel J, Seghatchian J, Tissot J, Lion N. Differences between calcium-stimulated and storage-induced erythrocyte-derived microvesicles. Transfus Apher Sci. 2015;53:153-8 pubmed publisher
    ..In addition to biophysical characterization, protein analysis is important to classify these cellular corpuscles and evaluate their potential impacts in diseases or transfusion medicine. ..
  48. Chejara D, Mabrouk M, Badhe R, Mulla J, Kumar P, Choonara Y, et al. A bio-injectable algin-aminocaproic acid thixogel with tri-stimuli responsiveness. Carbohydr Polym. 2016;135:324-33 pubmed publisher
    ..This approach of synthesizing a thixogels may be applicable to a broad variety of other natural polymers and has the potential for use in biomedical applications. ..
  49. Xia L, Wen H, Han X, Tang J, Huang Y. Luteinizing hormone inhibits cisplatin-induced apoptosis in human epithelial ovarian cancer cells. Oncol Lett. 2016;11:1943-1947 pubmed
    ..The present results suggest that LH affects the sensitivity of ovarian cancer cells to chemotherapy, primarily by signaling to inhibit apoptosis and to additionally suppress PDCD6. ..
  50. Rayl M, Truitt M, Held A, Sargeant J, Thorsen K, Hay J. Penta-EF-Hand Protein Peflin Is a Negative Regulator of ER-To-Golgi Transport. PLoS ONE. 2016;11:e0157227 pubmed publisher
    ..This work identifies for the first time a clear steady state role for a PEF protein in ER-to-Golgi transport-peflin is a negative regulator of transport. ..
  51. Subramanian L, Crabb J, Cox J, Durussel I, Walker T, Van Ginkel P, et al. Ca2+ binding to EF hands 1 and 3 is essential for the interaction of apoptosis-linked gene-2 with Alix/AIP1 in ocular melanoma. Biochemistry. 2004;43:11175-86 pubmed
    ..Together, these data indicate that gross surface hydrophobicity changes are insufficient for target recognition. ..
  52. Friand V, David G, Zimmermann P. Syntenin and syndecan in the biogenesis of exosomes. Biol Cell. 2015;107:331-41 pubmed publisher
    ..All these molecules appear to support the budding of SDC-syntenin and associated cargo into the lumen of endosomes. This highlights a major mechanism for the formation of intraluminal vesicles that will be released as exosomes. ..
  53. Hashemi M, Yousefi J, Hashemi S, Amininia S, Ebrahimi M, Taheri M, et al. Association between Programmed Cell Death 6 Interacting Protein Insertion/Deletion Polymorphism and the Risk of Breast Cancer in a Sample of Iranian Population. Dis Markers. 2015;2015:854621 pubmed publisher
    ..44, 95% CI = 0.30-0.63, p < 0.0001, D/I + I/I versus D/D) tested inheritance models. Also, the PDCD6IP I allele significantly decreased the risk of BC (OR = 0.59, 95% CI = 0.45-0.78, p < 0.001) compared to the D allele. ..
  54. Vergarajauregui S, Martina J, Puertollano R. Identification of the penta-EF-hand protein ALG-2 as a Ca2+-dependent interactor of mucolipin-1. J Biol Chem. 2009;284:36357-66 pubmed publisher
    ..Overall, our data provide new insight into the molecular mechanisms that regulate MCOLN1 activity. We propose that ALG-2 acts as a Ca(2+) sensor that modulates the function of MCOLN1 along the late endosomal-lysosomal pathway...
  55. He Y, Zhou B, Shi S, Zhang L, Li W. Genetic variation in PDCD6 and susceptibility to lung cancer. Asian Pac J Cancer Prev. 2012;13:4689-93 pubmed
    ..Genetic factors play an important role in its development. PDCD6, the encoding gene for programmed cell death protein 6, may function as a tumor suppressor gene...
  56. 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. ..
  57. Pitonak J, Galová J, Bernasovska J. Association of two selected polymorphisms with developed endometriosis in women from Slovakia. Bratisl Lek Listy. 2016;117:452-5 pubmed
    ..Polymorphism rs4957014 did not show any connection with development of endometriosis (Tab. 5, Ref. 10). ..
  58. Wang X, Zuo D, Yuan Y, Yang X, Hong Z, Zhang R. MicroRNA-183 promotes cell proliferation via regulating programmed cell death 6 in pediatric acute myeloid leukemia. J Cancer Res Clin Oncol. 2017;143:169-180 pubmed publisher
    ..Interestingly, miR-183 may function as an oncogene and may enhance cell proliferation by targeting PDCD6, implying a potential therapeutic target for this malignancy. ..
  59. Montaville P, Dai Y, Cheung C, Giller K, Becker S, Michalak M, et al. Nuclear translocation of the calcium-binding protein ALG-2 induced by the RNA-binding protein RBM22. Biochim Biophys Acta. 2006;1763:1335-43 pubmed
    ..More than 95% of the two proteins co-localized within the same area in the nucleus suggesting a functional interaction between the Ca(2+)-signaling protein ALG-2 and the RNA-binding protein RBM22. ..
  60. Inuzuka T, Inokawa A, Chen C, Kizu K, Narita H, Shibata H, et al. ALG-2-interacting Tubby-like protein superfamily member PLSCR3 is secreted by an exosomal pathway and taken up by recipient cultured cells. Biosci Rep. 2013;33:e00026 pubmed publisher
    ..Secreted Scr3 was taken up by HeLa cells, suggesting that Scr3 functions as a cell-to-cell transferable modulator carried by exosomes in a paracrine manner. ..
  61. Qin J, Yang Y, Gao S, Liu Y, Yu F, Zhou Y, et al. Deregulated ALG-2/HEBP2 axis alters microtubule dynamics and mitotic spindle behavior to stimulate cancer development. J Cell Physiol. 2017;232:3067-3076 pubmed publisher
    ..These finding thus uncover an important function for deregulated ALG-2/HEBP2 axis in cancer development by influencing microtubule dynamics and spindle behavior, providing novel insight into the etiology and pathogenesis of cancer. ..
  62. Takahara T, Inoue K, Arai Y, Kuwata K, Shibata H, Maki M. The calcium-binding protein ALG-2 regulates protein secretion and trafficking via interactions with MISSL and MAP1B proteins. J Biol Chem. 2017;292:17057-17072 pubmed publisher
    ..These results suggest that a change in the intracellular calcium level plays a role in regulation of the secretory pathway via interaction of ALG-2 with MISSL and MAP1B. ..
  63. Chen B, Borinstein S, Gillis J, Sykes V, Bogler O. The glioma-associated protein SETA interacts with AIP1/Alix and ALG-2 and modulates apoptosis in astrocytes. J Biol Chem. 2000;275:19275-81 pubmed
    ..Expression of the isolated SH3-N domain had the greatest effect in these experiments, indicating that interference in the interaction between endogenous SETA and AIP1 sensitizes astrocytes to apoptosis in response to DNA damage. ..
  64. Kitaura Y, Matsumoto S, Satoh H, Hitomi K, Maki M. Peflin and ALG-2, members of the penta-EF-hand protein family, form a heterodimer that dissociates in a Ca2+-dependent manner. J Biol Chem. 2001;276:14053-8 pubmed
    ..These results suggest that peflin has features common to those of other PEF proteins (dimerization and translocation to membranes) and may modulate the function of ALG-2 in Ca(2+) signaling. ..
  65. Shi S, Zhou B, Zhang K, Zhang L. Association between two single nucleotide polymorphisms of PDCD6 gene and increased endometriosis risk. Hum Immunol. 2013;74:215-8 pubmed publisher
    ..54, 95% CI=1.11-2.17). In conclusion, the current study indicates that PDCD6 gene may be a new susceptibility gene to endometriosis. ..
  66. Okumura M, Takahashi T, Shibata H, Maki M. Mammalian ESCRT-III-related protein IST1 has a distinctive met-pro repeat sequence that is essential for interaction with ALG-2 in the presence of Ca2+. Biosci Biotechnol Biochem. 2013;77:1049-54 pubmed
  67. Zhang D, Wang F, Pang Y, Zhao E, Zhu S, Chen F, et al. ALG2 regulates glioblastoma cell proliferation, migration and tumorigenicity. Biochem Biophys Res Commun. 2017;486:300-306 pubmed publisher
    ..039). We found that over-expression of ALG2 in glioblastoma could inhibit cell proliferation and, conversely, that down-regulation of ALG2 could promote cell ..
  68. 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. ..
  69. Hansen C, Tarabykina S, la Cour J, Lollike K, Berchtold M. The PEF family proteins sorcin and grancalcin interact in vivo and in vitro. FEBS Lett. 2003;545:151-4 pubmed
    ..Our results indicate that heterodimerization, in addition to differential interactions with target proteins, might be a way to regulate and fine tune processes mediated by calcium binding proteins of the penta-EF hand type. ..
  70. Takahara T, Arai Y, Kono Y, Shibata H, Maki M. A microtubule-associated protein MAP1B binds to and regulates localization of a calcium-binding protein ALG-2. Biochem Biophys Res Commun. 2018;497:492-498 pubmed publisher
    ..Thus, these results suggest that MAP1B plays a role in regulation of ALG-2 and Sec31A localizations, and that dysregulation of calcium-dependent binding of ALG-2 to MAP1B might influence pathological conditions such as cancers. ..
  71. Krebs J, Saremaslani P, Caduff R. ALG-2: a Ca2+ -binding modulator protein involved in cell proliferation and in cell death. Biochim Biophys Acta. 2002;1600:68-73 pubmed
    ..The role of ALG-2 as a possible clinical marker and, molecularly, as a possible modulator at the interface between cell proliferation and cell death is discussed. ..
  72. Zhou B, Zhang P, Tang T, Zhang K, Wang Y, Song Y, et al. Prognostic value of PDCD6 polymorphisms and the susceptibility to bladder cancer. Tumour Biol. 2014;35:7547-54 pubmed publisher
    ..93, P?=?0.03). PDCD6 may represent a biomarker candidate gene that could help to identify a group of patients at high risk for recurrence and death. ..
  73. Rios C, Warren D, Olson B, Abbott A. Functional analysis of microRNA pathway genes in the somatic gonad and germ cells during ovulation in C. elegans. Dev Biol. 2017;426:115-125 pubmed publisher
    ..These data identify specific steps in the process of ovulation that require miRNA pathway gene activity in the somatic gonad cells. ..
  74. Tarabykina S, Møller A, Durussel I, Cox J, Berchtold M. Two forms of the apoptosis-linked protein ALG-2 with different Ca(2+) affinities and target recognition. J Biol Chem. 2000;275:10514-8 pubmed
    ..Pellegrini, L., Guiet, C., and D'Adamio, L. (1999) J. Biol. Chem. 274, 1533-1540). We propose that the minor sequence difference between ALG-2,5 and ALG-2,1 affects the Ca(2+) binding properties and function of the proteins. ..
  75. Chatellard Causse C, Blot B, Cristina N, Torch S, Missotten M, Sadoul R. Alix (ALG-2-interacting protein X), a protein involved in apoptosis, binds to endophilins and induces cytoplasmic vacuolization. J Biol Chem. 2002;277:29108-15 pubmed
    ..This vacuolization phenomenon is greatly enhanced upon co-expression with endophilins and may be part of the protecting mechanism afforded by Alix-CT. ..
  76. Hwang I, Jung Y, Kim E. Interaction of ALG-2 with ASK1 influences ASK1 localization and subsequent JNK activation. FEBS Lett. 2002;529:183-7 pubmed
    ..This study reports that ALG-2 could regulate the subcellular localization and the JNK activity modulation of ASK1 by direct interaction. ..
  77. Ichioka F, Takaya E, Suzuki H, Kajigaya S, Buchman V, Shibata H, et al. HD-PTP and Alix share some membrane-traffic related proteins that interact with their Bro1 domains or proline-rich regions. Arch Biochem Biophys. 2007;457:142-9 pubmed
    ..While Alix associated with both ALG-2 and TSG101 in a Ca2+-dependent manner, HD-PTP interacted with ALG-2 Ca2+-dependently but with TSG101 Ca2+-independently. ..
  78. Suzuki H, Kawasaki M, Kakiuchi T, Shibata H, Wakatsuki S, Maki M. Crystallization and X-ray diffraction analysis of N-terminally truncated human ALG-2. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008;64:974-7 pubmed publisher
    ..Although both crystals contained eight ALG-2 molecules per asymmetric unit, the metal-ion locations and octameric arrangements were found to be significantly different. ..
  79. Su D, Xu H, Feng J, Gao Y, Gu L, Ying L, et al. PDCD6 is an independent predictor of progression free survival in epithelial ovarian cancer. J Transl Med. 2012;10:31 pubmed publisher
    ..Further studies are needed to more completely elucidate the molecular mechanisms of PDCD6 involve in ovarian cancer progression. ..
  80. Zhou B, Bai P, Xue H, Zhang Z, Shi S, Zhang K, et al. Single nucleotide polymorphisms in PDCD6 gene are associated with the development of cervical squamous cell carcinoma. Fam Cancer. 2015;14:1-8 pubmed publisher
    ..044, OR = 1.414). Our results suggest that these two tag SNPs of PDCD6 are associated with CSCC, indicating that PDCD6 may play an important role in the pathogenesis of CSCC. ..
  81. 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
    ..The function of ALG-2·HEBP2 complex in HIV-1 replication was further explored. ALG-2 inhibits HIV-1 production by affecting Gag expression and distribution, and HEBP2 might aid this process by tethering ALG-2 in the cytoplasm. ..
  82. Salvia R, Grossi G, Amoresano A, Scieuzo C, Nardiello M, Giangrande C, et al. The multifunctional polydnavirus TnBVANK1 protein: impact on host apoptotic pathway. Sci Rep. 2017;7:11775 pubmed publisher
    ..virescens haemocytes. Collectively, these results indicate that TnBVANK1 induces apoptosis by interacting with Alix, suggesting a role of TnBVANK1 in the suppression of host immune response observed after parasitisation by T. nigriceps. ..
  83. 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. ..
  84. Yoon J, Choi Y, Kim S, Nam S, Lee J, Park W. Programmed cell death 6 (PDCD6) as a prognostic marker for gastric cancers. Tumour Biol. 2012;33:485-94 pubmed publisher
    ..001). These data provide evidence that the PDCD6 gene is a significant prognostic biomarker for advanced gastric cancer patients. ..
  85. 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. ..
  86. Sadoul R, Laporte M, Chassefeyre R, Chi K, Goldberg Y, Chatellard C, et al. The role of ESCRT during development and functioning of the nervous system. Semin Cell Dev Biol. 2018;74:40-49 pubmed publisher
    ..The necessity of ESCRT for the harmonious function of the brain has its pathological counterpart, the mutations in CHMP2B of ESCRT-III giving rise to several neurodegenerative diseases. ..
  87. Krebs J, Klemenz R. The ALG-2/AIP-complex, a modulator at the interface between cell proliferation and cell death? A hypothesis. Biochim Biophys Acta. 2000;1498:153-61 pubmed
    ..The two proteins interact with each other in a Ca(2+)-dependent manner, and the role of the complex ALG-2/AIP as a possible modulator at the interface between cell proliferation and cell death is discussed. ..
  88. Satoh H, Shibata H, Nakano Y, Kitaura Y, Maki M. ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca(2+)-dependent manner. Biochem Biophys Res Commun. 2002;291:1166-72 pubmed
  89. 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
    ..Co-transfection of PDCD6 and DAPk1 cDNA into a tumor cell line accelerated apoptosis via caspase-3 dependent pathway. ..
  90. Li X, Rydzewski N, Hider A, Zhang X, Yang J, Wang W, et al. A molecular mechanism to regulate lysosome motility for lysosome positioning and tubulation. Nat Cell Biol. 2016;18:404-17 pubmed publisher
    ..Ca(2+) release from lysosomes thus provides an on-demand mechanism regulating lysosome motility, positioning and tubulation. ..
  91. Kaul Z, Chakrabarti O. Tumor susceptibility gene 101 regulates predisposition to apoptosis via ESCRT machinery accessory proteins. Mol Biol Cell. 2017;28:2106-2122 pubmed publisher
  92. Brown K, Svendsen J, Tucci R, Montgomery B, Montgomery T. ALG-5 is a miRNA-associated Argonaute required for proper developmental timing in the Caenorhabditis elegans germline. Nucleic Acids Res. 2017;45:9093-9107 pubmed publisher
    ..Our results provide a near-comprehensive analysis of miRNA-Argonaute interactions in C. elegans and reveal a new role for miRNAs in the germline. ..