ALG2

Summary

Gene Symbol: ALG2
Description: ALG2, alpha-1,3/1,6-mannosyltransferase
Alias: CDG1I, CDGIi, CMS14, CMSTA3, NET38, hALPG2, alpha-1,3/1,6-mannosyltransferase ALG2, GDP-Man:Man(1)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase, GDP-Man:Man(1)GlcNAc(2)-PP-dolichol mannosyltransferase, GDP-Man:Man(2)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase, alpha-1,3-mannosyltransferase ALG2, asparagine-linked glycosylation 2 homolog (S. cerevisiae, alpha-1,3-mannosyltransferase), asparagine-linked glycosylation 2 homolog (yeast, alpha-1,3-mannosyltransferase), asparagine-linked glycosylation 2, alpha-1,3-mannosyltransferase homolog, asparagine-linked glycosylation protein 2 homolog, homolog of yeast ALG2
Species: human
Products:     ALG2

Top Publications

  1. 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. ..
  2. Helm J, Bentley M, Thorsen K, Wang T, Foltz L, Oorschot V, et al. Apoptosis-linked gene-2 (ALG-2)/Sec31 interactions regulate endoplasmic reticulum (ER)-to-Golgi transport: a potential effector pathway for luminal calcium. J Biol Chem. 2014;289:23609-28 pubmed publisher
    ..These results represent the first outline of a mechanism that connects luminal calcium to specific protein interactions regulating vesicle trafficking machinery. ..
  3. la Cour J, Høj B, Mollerup J, Simon R, Sauter G, Berchtold M. The apoptosis linked gene ALG-2 is dysregulated in tumors of various origin and contributes to cancer cell viability. Mol Oncol. 2008;1:431-9 pubmed publisher
    ..siRNA mediated ALG-2 downregulation led to a significant reduction in viability of HeLa cells indicating that ALG-2 may contribute to tumor development and expansion. ..
  4. 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. ..
  5. 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. ..
  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. 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. ..
  8. Høj B, la Cour J, Mollerup J, Berchtold M. ALG-2 knockdown in HeLa cells results in G2/M cell cycle phase accumulation and cell death. Biochem Biophys Res Commun. 2009;378:145-8 pubmed publisher
    ..Thus, our results indicate that ALG-2 has an anti-apoptotic function in HeLa cells by facilitating the passage through checkpoints in the G2/M cell cycle phase. ..
  9. la Cour J, Schindler A, Berchtold M, Schekman R. ALG-2 attenuates COPII budding in vitro and stabilizes the Sec23/Sec31A complex. PLoS ONE. 2013;8:e75309 pubmed publisher
    ..These results introduce a regulatory role for ALG-2/Ca(2+) in COPII tethering and vesicle budding. ..

More Information

Publications45

  1. Shibata H, Inuzuka T, Yoshida H, Sugiura H, Wada I, Maki M. The ALG-2 binding site in Sec31A influences the retention kinetics of Sec31A at the endoplasmic reticulum exit sites as revealed by live-cell time-lapse imaging. Biosci Biotechnol Biochem. 2010;74:1819-26 pubmed
  2. Thiel C, Schwarz M, Peng J, Grzmil M, Hasilik M, Braulke T, et al. A new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharide biosynthesis. J Biol Chem. 2003;278:22498-505 pubmed
    ..Because the Saccharomyces cerevisiae mutant alg2-1 was known to accumulate the same shortened dolichol-linked oligosaccharides as the patient, the yeast ALG2 ..
  3. Mahul Mellier A, Strappazzon F, Petiot A, Chatellard Causse C, Torch S, Blot B, et al. Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death. J Biol Chem. 2008;283:34954-65 pubmed publisher
    ..Taken together, these results highlight Alix and ALG-2 as new actors of the TNF-R1 pathway. ..
  4. 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. ..
  5. 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. ..
  6. Osugi K, Suzuki H, Nomura T, Ariumi Y, Shibata H, Maki M. Identification of the P-body component PATL1 as a novel ALG-2-interacting protein by in silico and far-Western screening of proline-rich proteins. J Biochem. 2012;151:657-66 pubmed publisher
    ..Furthermore, in immunofluorescence microscopic analyses, PATL1 as well as DCP1A, a well-known P-body marker, co-localized with a subset of ALG-2. This is the first report showing interaction of ALG-2 with a P-body component. ..
  7. 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. ..
  8. 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. ..
  9. 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. ..
  10. Ram B, Ramakrishna G. Endoplasmic reticulum vacuolation and unfolded protein response leading to paraptosis like cell death in cyclosporine A treated cancer cervix cells is mediated by cyclophilin B inhibition. Biochim Biophys Acta. 2014;1843:2497-512 pubmed publisher
    ..eventually undergo cell death which lacked the typical apoptotic features, but showed significant decrease in AIP (ALG2 interacting protein) as seen in paraptosis...
  11. Engel A. Congenital Myasthenic Syndromes in 2018. Curr Neurol Neurosci Rep. 2018;18:46 pubmed publisher
    ..The identified disease proteins are SNAP25B, synaptotagmin 2, Munc13-1, synaptobrevin-1, GFPT1, DPAGT1, ALG2, ALG14, Agrin, GMPPB, LRP4, myosin 9A, collagen 13A1, the mitochondrial citrate carrier, PREPL, LAMA5, the ..
  12. Cheng B, Du Y, Wen Y, Zhao Y, He A, Ding M, et al. Integrative analysis of genome-wide association study and chromosomal enhancer maps identified brain region related pathways associated with ADHD. Compr Psychiatry. 2018;88:65-69 pubmed publisher
    ..We detected several candidate genes for ADHD, such as AHI1, ALG2 and DNM1...
  13. Asteggiano C, Papazoglu M, Bistué Millón M, Peralta M, Azar N, Spécola N, et al. Ten years of screening for congenital disorders of glycosylation in Argentina: case studies and pitfalls. Pediatr Res. 2018;84:837-841 pubmed publisher
    ..Seven patients showed a type 1 pattern: four with PMM2-CDG, two with ALG2-CDG, and one with classical galactosemia...
  14. Li S, Wang N, Xu X, Fujita M, Nakanishi H, Kitajima T, et al. Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase. FASEB J. 2018;32:2492-2506 pubmed publisher
    ..The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-..
  15. Belaya K, Rodríguez Cruz P, Liu W, Maxwell S, McGowan S, Farrugia M, et al. Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies. Brain. 2015;138:2493-504 pubmed publisher
    ..Mutations in at least 20 genes are known to lead to the onset of these conditions. Four of these, ALG2, ALG14, DPAGT1 and GFPT1, are involved in glycosylation...
  16. Engel A. Genetic basis and phenotypic features of congenital myasthenic syndromes. Handb Clin Neurol. 2018;148:565-589 pubmed publisher
    ..Other less frequently identified disease genes include LAMB2, AGRN, LRP4, MUSK, GFPT1, DPAGT1, ALG2, and ALG 14 as well as SCN4A, PREPL, PLEC1, DNM2, and MTM1...
  17. Cordts I, Funk F, Schulz J, Weis J, Claeys K. Tubular aggregates in autoimmune Lambert-Eaton myasthenic syndrome. Neuromuscul Disord. 2016;26:880-884 pubmed publisher
    ..a limb-girdle myasthenia with tubular aggregates was suspected, but genetic analyses of GFPT1, DPGAT1, and ALG2 were normal. Two years later, the patient presented with progressive weakness and autonomic dysfunction...
  18. 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
    ..Here, we show that CUL3 and its adaptor KLHL12 require two calcium-binding proteins, PEF1 and ALG2, for recognition of their substrate SEC31...
  19. Lombard J. The multiple evolutionary origins of the eukaryotic N-glycosylation pathway. Biol Direct. 2016;11:36 pubmed publisher
    ..one gene of the glycosyltransferase 1 (GT1) superfamily and Stt3 have proteoarchaeal (TACK superphylum) origins; alg2/alg11 may have resulted from the duplication of the original GT1 gene; the lumen glycosyltransferases were probably ..
  20. Monies D, Alhindi H, Almuhaizea M, Abouelhoda M, Alazami A, Goljan E, et al. A first-line diagnostic assay for limb-girdle muscular dystrophy and other myopathies. Hum Genomics. 2016;10:32 pubmed
    ..Non-LGMD myopathies were due to mutations in genes associated with congenital disorder of glycosylation (ALG2), rigid spine muscular dystrophy 1 (SEPN1), inclusion body myopathy2/Nonaka myopathy (GNE), and neuropathy (WNK1)...
  21. 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. ..
  22. Cossins J, Belaya K, Hicks D, Salih M, Finlayson S, Carboni N, et al. Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. Brain. 2013;136:944-56 pubmed publisher
    ..We identify ALG14 and ALG2 as novel genes in which mutations cause a congenital myasthenic syndrome...
  23. Jaeken J. Congenital disorders of glycosylation (CDG): update and new developments. J Inherit Metab Dis. 2004;27:423-6 pubmed
    ..It was concluded that we are still at the beginning of 'explosive' research on CDG and that we need to apply new and known technologies to the diagnosis, understanding of pathophysiology, and treatment of CDG. ..
  24. 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. ..
  25. 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
  26. 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. ..
  27. Jaeken J, Carchon H. Congenital disorders of glycosylation: a booming chapter of pediatrics. Curr Opin Pediatr. 2004;16:434-9 pubmed
    ..Therefore, it is strongly recommended that congenital disorders of glycosylation be considered in any child with an unexplained clinical syndrome. ..
  28. Wan M, Wu X, Guan K, Han M, Zhuang Y, Xu T. Muscle atrophy in transgenic mice expressing a human TSC1 transgene. FEBS Lett. 2006;580:5621-7 pubmed
    ..This study suggests that an increase in the steady state level of resident TSC1-TSC2 complex is sufficient to reduce muscle mass and cause atrophy. ..
  29. Viding E, Price T, Jaffee S, Trzaskowski M, Davis O, Meaburn E, et al. Genetics of callous-unemotional behavior in children. PLoS ONE. 2013;8:e65789 pubmed publisher
    ..This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU. ..
  30. 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. ..
  31. 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
  32. 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. ..
  33. Schmidt M, Chen B, Randazzo L, Bogler O. SETA/CIN85/Ruk and its binding partner AIP1 associate with diverse cytoskeletal elements, including FAKs, and modulate cell adhesion. J Cell Sci. 2003;116:2845-55 pubmed
  34. Draeby I, Woods Y, la Cour J, Mollerup J, Bourdon J, Berchtold M. The calcium binding protein ALG-2 binds and stabilizes Scotin, a p53-inducible gene product localized at the endoplasmic reticulum membrane. Arch Biochem Biophys. 2007;467:87-94 pubmed
    ..In vitro and in vivo binding of ALG-2 to Scotin was demonstrated to be strictly calcium dependent indicating a role of this interaction in calcium signaling pathways. ..
  35. 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 ..
  36. Lim Y, Mantalaris A, Yap M, Wong D. Simultaneous targeting of Requiem & Alg-2 in Chinese hamster ovary cells for improved recombinant protein production. Mol Biotechnol. 2010;46:301-7 pubmed publisher
    ..This in turn led to an approximately 1.5-fold increase in recombinant protein productivity. ..