Affinage

ALG2

Alpha-1,3/1,6-mannosyltransferase ALG2 · UniProt Q9H553

Length
416 aa
Mass
47.1 kDa
Annotated
2026-04-28
100 papers in source corpus 50 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ALG2/PDCD6 encodes a penta-EF-hand calcium-sensor protein that functions as a Ca²⁺-dependent adaptor linking membrane-trafficking machinery to diverse cellular processes including ER-to-Golgi secretion, endosomal sorting, lysosomal resilience, membrane repair, innate immune signaling, and apoptosis. Upon Ca²⁺ binding, ALG-2 undergoes a conformational change exposing hydrophobic pockets and membrane-binding surfaces that enable it to bridge COPII coat components (Sec31A, TFG, MISSL) at ER exit sites—stabilizing Sec31A retention and modulating vesicle budding—and to bridge ESCRT machinery (ALIX, TSG101, VPS37B/C) at endosomes and lysosomes, where it relieves ALIX autoinhibition to promote ubiquitinated EGFR MVB sorting and recruits ESCRT proteins to maintain lysosomal membrane integrity (PMID:16957052, PMID:24069399, PMID:27462417, PMID:38781205). ALG-2 also enters the nucleus where it interacts with CHERP at nuclear speckles to regulate alternative splicing of IP3R1 pre-mRNA, suppresses STING ER-to-vesicle trafficking to attenuate type I interferon responses, and participates in T cell apoptosis through proteasome-mediated MCL1 degradation and FasL vesicular transport (PMID:24078636, PMID:34787301, PMID:31919392, PMID:32766719). Separately, the ALG2 mannosyltransferase (same gene symbol, distinct protein) catalyzes sequential α1,3- and α1,6-mannosylation in dolichol-linked oligosaccharide biosynthesis, and loss-of-function mutations cause congenital disorder of glycosylation type Ii and congenital myasthenic syndrome (PMID:12684507, PMID:16878994, PMID:23404334).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1996 High

    Establishing that ALG-2 is a Ca²⁺-binding protein required for programmed cell death resolved a key unknown—whether Ca²⁺-sensing proteins mediate receptor-triggered apoptosis—by showing that ALG-2 depletion protects T cells from TCR-, Fas-, and glucocorticoid-induced death.

    Evidence Functional death-trap selection and antisense depletion in T cell hybridoma with apoptosis readout

    PMID:8560270

    Open questions at the time
    • Downstream targets of ALG-2 in apoptosis were unknown
    • Whether ALG-2 acts cell-autonomously or through secreted signals was unclear
  2. 1997 High

    Placing ALG-2 genetically downstream of caspase activation answered whether ALG-2 operated in the canonical caspase cascade, establishing it as a post-caspase or parallel effector rather than a caspase activator.

    Evidence ALG-2 antisense depletion with PARP cleavage and fluorogenic caspase substrate assays showing intact caspase activity but blocked death

    PMID:9164928

    Open questions at the time
    • Identity of ALG-2's downstream effectors remained unknown
    • Whether ALG-2 acts on membrane integrity or nuclear apoptosis was unresolved
  3. 1999 High

    Discovery of the Ca²⁺-dependent ALG-2–ALIX interaction and ALG-2 homodimerization via the fifth EF-hand established the first protein partner and the oligomeric framework for ALG-2 function, answering how Ca²⁺ is transduced into protein–protein interactions.

    Evidence Yeast two-hybrid, co-immunoprecipitation, gel filtration, and Ca²⁺-binding mutagenesis (E47A/E114A)

    PMID:10200558 PMID:10360947 PMID:9880530

    Open questions at the time
    • Structural basis of Ca²⁺-induced conformational change was unknown
    • Cellular function of the ALG-2–ALIX complex was not established
  4. 1998 High

    Demonstration that Ca²⁺ binding induces hydrophobic surface exposure on ALG-2 provided the biophysical mechanism by which Ca²⁺ triggers partner recruitment, answering why ALG-2 interactions are Ca²⁺-dependent.

    Evidence TNS fluorescence spectroscopy with recombinant ALG-2, showing half-maximal hydrophobic exposure at ~6 µM Ca²⁺

    PMID:9832622

    Open questions at the time
    • Which specific hydrophobic surfaces were exposed was unresolved until crystallography
  5. 2001 High

    The crystal structure of Ca²⁺-loaded ALG-2 revealed Ca²⁺ occupancy at EF1, EF3, and EF5 and a rigid-body rotation exposing a hydrophobic cleft, providing the atomic-level explanation for Ca²⁺-dependent target recognition.

    Evidence X-ray crystallography at 2.3 Å resolution

    PMID:11525164

    Open questions at the time
    • No co-crystal with any binding partner was available
    • How ALG-2 discriminates between different targets structurally was unknown
  6. 2001 High

    Discovery that peflin forms a Ca²⁺-sensitive heterodimer with ALG-2 that dissociates upon Ca²⁺ addition established an additional layer of regulation—ALG-2 is sequestered by peflin at low Ca²⁺ and liberated for target engagement at high Ca²⁺.

    Evidence Co-immunoprecipitation, gel filtration, and subcellular fractionation in Jurkat cells

    PMID:11278427

    Open questions at the time
    • Functional consequence of peflin–ALG-2 heterodimer dissociation for any specific cellular process was unknown
  7. 2003 High

    Identification of hALG2 as an α1,3-mannosyltransferase deficient in CDG-Ii patients—rescued by wild-type expression in both human fibroblasts and yeast—established the enzymatic function and disease relevance of the glycosyltransferase ALG2, distinct from the PDCD6 Ca²⁺-sensor.

    Evidence Mannosyltransferase activity assay in patient fibroblast extracts and complementation of yeast alg2-1

    PMID:12684507

    Open questions at the time
    • Whether ALG2 catalyzes one or both mannosylation steps was unresolved
    • Structural basis of catalysis was unknown
  8. 2004 High

    Mapping the ALG-2–ALIX binding interface to four PxY repeats in ALIX's Pro-rich region, and showing ALG-2 binds TSG101 and co-localizes with aberrant endosomes, connected ALG-2 to the ESCRT pathway for the first time and answered how ALG-2 accesses endosomal function.

    Evidence Yeast two-hybrid, biotin-ALG-2 overlay, GST pulldown, alanine mutagenesis of PxY motifs, immunofluorescence with BAPTA

    PMID:14999017 PMID:16004603

    Open questions at the time
    • Whether ALG-2 actively bridges ALIX and TSG101 or binds them independently was unclear
    • Functional role in MVB sorting was not yet tested
  9. 2006 High

    Discovery that ALG-2 is recruited to ER exit sites by binding Sec31A and stabilizes COPII coat retention established a major new cellular role for ALG-2 in ER-to-Golgi transport, answering how Ca²⁺ signaling intersects with secretory pathway regulation.

    Evidence Co-IP, RNAi, Ca²⁺ ionophore/chelator treatments, confocal microscopy, and live-cell imaging showing ALG-2 dynamics track Ca²⁺ oscillations

    PMID:16957052 PMID:17196169 PMID:17214967

    Open questions at the time
    • Whether ALG-2 promotes or inhibits COPII budding was unresolved
    • Identity of additional ERES partners was unknown
  10. 2006 High

    In vitro reconstitution proved yeast Alg2 is a bifunctional enzyme catalyzing sequential α1,3- then α1,6-mannosylation to form the first branched Man₃GlcNAc₂-PP-Dol, resolving a longstanding ambiguity about whether one or two enzymes perform these steps.

    Evidence In vitro mannosyltransferase assay with recombinant Alg2 and defined dolichylpyrophosphate-linked substrates

    PMID:16878994

    Open questions at the time
    • Human ALG2 kinetic order preference was not yet established
    • Structural basis of bifunctionality unknown
  11. 2009 High

    Reconstitution showing ALG-2 dimers physically bridge ALIX and TSG101 answered whether ALG-2 is a passive Ca²⁺-sensor or an active scaffold, establishing its adaptor function within the ESCRT network.

    Evidence Strep-tag pulldown, ALG-2 knockdown, recombinant ALG-2 add-back, dimerization-defective mutant analysis

    PMID:19520058

    Open questions at the time
    • Which ESCRT-I subunits are primarily contacted was not fully resolved
    • In vivo relevance for MVB cargo sorting was untested
  12. 2013 High

    Multiple discoveries simultaneously expanded ALG-2's functional reach: nuclear ALG-2 interacts with CHERP to regulate IP3R1 alternative splicing, ALG2 mutations cause congenital myasthenic syndrome, and an in vitro COPII budding assay showed ALG-2/Ca²⁺ attenuates vesicle budding by bridging Sec31A to Sec23—collectively establishing ALG-2 as both a secretory pathway regulator and a nuclear splicing co-factor, and linking the glycosyltransferase to neuromuscular disease.

    Evidence In vitro COPII budding assay with EF1 mutant; co-IP plus siRNA knockdown with RT-PCR splicing readout; patient exome sequencing with protein expression validation

    PMID:23404334 PMID:24069399 PMID:24078636

    Open questions at the time
    • How ALG-2 is imported into the nucleus mechanistically was unclear
    • Whether splicing regulation requires ALIX was not tested
    • ALG2 CMS therapeutic rescue was not demonstrated
  13. 2015 High

    Crystal structures of ALG-2 bound to Sec31A versus ALIX peptides revealed that these partners bind to structurally distinct hydrophobic pockets (Pocket 3 vs. Pockets 1/2), with separation-of-function mutations (F85A, Y180A) proving target discrimination—answering how one small adaptor binds multiple partners selectively.

    Evidence X-ray crystallography of ALG-2–Sec31A peptide complex, alanine mutagenesis of pocket residues, pulldown assays

    PMID:25667979 PMID:27462417

    Open questions at the time
    • Whether simultaneous binding of two different targets occurs on a single dimer was untested
    • Structural basis of ESCRT-I binding not resolved
  14. 2016 High

    Identification of TFG and MISSL as additional ALG-2 partners at ERES that regulate ER-to-Golgi transport demonstrated that ALG-2 coordinates a network of ERES factors rather than acting solely through Sec31A.

    Evidence Live-cell imaging, Ca²⁺ mobilization, in vitro cross-linking polymerization of TFG, SEAP secretion and procollagen transport assays with siRNA knockdown

    PMID:27813252 PMID:28864773

    Open questions at the time
    • Hierarchy among ALG-2 ERES partners unknown
    • Whether peflin regulates TFG/MISSL interactions was untested
  15. 2018 High

    Demonstrating that ALG-2 knockout cells are sensitized to plasma membrane damage and that protection requires both Ca²⁺-binding and ALIX interaction established ALG-2 as a Ca²⁺-triggered membrane repair factor, expanding its role beyond trafficking.

    Evidence ALG-2 gene knockout in DT-40 cells, electroporation and digitonin survival assays, Ca²⁺-binding mutant and ALIX-blocking peptide

    PMID:30240438

    Open questions at the time
    • Whether ESCRT-III is the downstream effector of repair was not directly shown
    • Relevance in mammalian primary cells not tested
  16. 2020 Medium

    Multiple studies connected ALG-2 to T cell immune regulation through distinct mechanisms—proteasome-mediated MCL1 degradation (via Rpn3 binding) and FasL vesicular transport—explaining how ALG-2 promotes apoptosis during immune contraction.

    Evidence Co-IP of ALG-2 with Rpn3, proteasome activity and MCL1 stability assays, ALG-2 knockdown in T cells; Co-IP of ALG-2 with FasL, FasL trafficking readout

    PMID:31919392 PMID:32766719

    Open questions at the time
    • Relative contribution of proteasome vs. FasL pathways to T cell death not quantified
    • In vivo immune phenotype of ALG-2 deficiency not established
    • Rpn3 interaction awaits independent replication
  17. 2021 High

    Establishing that ALG-2 suppresses STING ER-to-vesicle trafficking in a Ca²⁺-dependent manner, with knockout cells showing enhanced type I IFN signaling, placed ALG-2 as a negative regulator of innate immunity and answered how Ca²⁺ sensing intersects with antiviral defense.

    Evidence ALG-2 knockout in THP-1 cells, co-IP, immunofluorescence trafficking assay, Ca²⁺-binding mutant, HSV-1 and cGAMP stimulation

    PMID:34787301

    Open questions at the time
    • Mechanism by which ALG-2 retains STING in the ER is unclear
    • Whether ALIX or ESCRT is involved was not tested
  18. 2021 High

    Demonstrating that the ALG-2/peflin heterodimer buffers secretion at steady state while Ca²⁺ signals shift the balance toward peflin-free ALG-2 complexes that stimulate secretion resolved the apparent contradiction of ALG-2 sometimes promoting and sometimes inhibiting COPII function.

    Evidence Peflin/ALG-2 double-knockdown epistasis, SEAP and collagen I secretion assays, ERES fractionation in NRK and PC12 cells

    PMID:34762908

    Open questions at the time
    • Quantitative Ca²⁺ thresholds for heterodimer vs. homodimer switching unknown
    • Whether peflin regulates ESCRT-related functions was untested
  19. 2022 High

    Kinetic analysis of purified human ALG2 confirmed the α1,3-before-α1,6 mannosylation order under physiological conditions and revealed a single membrane-anchoring domain (unlike yeast), resolving species-specific topology differences.

    Evidence LC-MS quantitative kinetics with purified hAlg2 and defined LLO substrates, topology analysis

    PMID:35136180

    Open questions at the time
    • No crystal structure of human ALG2 mannosyltransferase available
    • Regulation of catalytic activity in vivo is unknown
  20. 2024 High

    Three landmark studies resolved how ALG-2 reaches membranes—via direct electrostatic/hydrophobic membrane binding distinct from protein-mediated recruitment—and established new functional roles at lysosomes (ESCRT-dependent resilience to osmotic stress) and in nutrient-stress-triggered ERES microautophagy requiring ALG-2, ALIX, and ubiquitinated SEC31.

    Evidence GUV membrane binding, MD simulations, charge-reversal mutagenesis, lysosomal leakage assays with ΔGF122 variant, super-resolution imaging, FIB-SEM, in vitro GUV reconstitution of ERES microautophagy, ALG-2 knockout

    PMID:38386713 PMID:38593803 PMID:38781205

    Open questions at the time
    • Whether ERES microautophagy is selective for specific cargoes is unknown
    • Relative contribution of direct membrane binding vs. protein-mediated recruitment in vivo is unquantified
    • Whether lysosomal resilience function is relevant in disease settings remains untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of ALG-2 bridging ESCRT-I subunits (no ESCRT-I co-crystal), whether ALG-2 functions overlap or are separable in vivo (no animal knockout phenotype published), and how ALG-2 nuclear import is regulated.
  • No ALG-2 knockout mouse or in vivo phenotyping reported
  • No co-crystal structure of ALG-2 with full-length ALIX or ESCRT-I
  • Mechanism of ALG-2 nuclear import unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0016740 transferase activity 4 GO:0008289 lipid binding 1
Localization
GO:0005783 endoplasmic reticulum 5 GO:0005764 lysosome 3 GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005768 endosome 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-1430728 Metabolism 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-392499 Metabolism of proteins 2 R-HSA-9612973 Autophagy 2 R-HSA-168256 Immune System 1
Partners
CHERPMCOLN1PDCD6IPPEF1SEC31ASTING1TFGTSG101
Complex memberships
ALG-2 homodimerALG-2/peflin heterodimerAlg1/Alg2/Alg11 mannosyltransferase complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 ALG-2 is a Ca2+-binding protein required for T cell receptor-, Fas-, and glucocorticoid-induced cell death; depletion of ALG-2 protects T cell hybridoma from apoptosis, placing ALG-2 as a required mediator of Ca2+-regulated death signals. Functional selection/death trap assay, antisense depletion with apoptosis readout Science High 8560270
1997 ALG-2 functions downstream of ICE/Ced-3 caspase activation in apoptosis; ALG-2-depleted cells still activate caspases normally (cleave PARP) yet do not die, placing ALG-2 downstream of or independent of caspases. ALG-2 antisense depletion combined with fluorogenic and PARP substrate caspase activity assays Journal of Immunology High 9164928
1999 ALG-2 directly interacts with AIP1 (Alix) in a strictly Ca2+-dependent manner; both proteins co-localize in the cytosol, and overexpression of a truncated AIP1 protects cells from trophic-factor withdrawal death. Yeast two-hybrid screen, co-immunoprecipitation, subcellular co-localization The Journal of Biological Chemistry High 9880530
1999 ALG-2 binds to itself (Ca2+-independent homodimerization) and to Alix (Ca2+-dependent); the fifth EF-hand participates in dimer formation as shown by biochemical and gel-filtration analysis. Yeast two-hybrid, co-immunoprecipitation, gel filtration Cell Death and Differentiation High 10200558
1998 Ca2+ binding induces exposure of a hydrophobic surface on ALG-2 in a concentration-dependent manner (~6 µM half-maximal), a conformational change that is Mg2+-insensitive and drives association with macromolecules in cells. Fluorescent hydrophobicity probe (TNS) spectroscopy, recombinant protein characterization Journal of Biochemistry High 9832622
1999 ALG-2 possesses two high-affinity Ca2+-binding sites and one low-affinity site; Ca2+ binding to both strong sites is required for Ca2+-induced aggregation; the fifth EF-hand mediates homodimerization. Gel filtration, chemical cross-linking, mutagenesis (E47A/E114A), fluorescence spectroscopy, circular dichroism Biochemistry High 10360947
2000 Two alternatively spliced isoforms of ALG-2 exist (ALG-2,5 and ALG-2,1, differing by Gly121-Phe122); ALG-2,1 lacks the ability to interact with AIP1 and has a higher Ca2+-binding affinity, demonstrating that two residues govern target specificity. Yeast two-hybrid, Ca2+ binding assays, sequence analysis of isoforms The Journal of Biological Chemistry High 10744743
2001 X-ray crystal structure of Ca2+-loaded ALG-2 (des1-20, 2.3 Å) reveals five EF-hand fold with Ca2+ bound to EF1, EF3, and EF5; Ca2+ induces a rigid-body rotation of EF1-2 relative to EF4-5, exposing a hydrophobic cleft that accepts a Gly/Pro-rich peptide. X-ray crystallography at 2.3 Å resolution Structure High 11525164
2001 Peflin forms a heterodimer with ALG-2 in Jurkat cells; the heterodimer dissociates upon Ca2+ addition, and peflin translocates to membranes/cytoskeleton in the presence of Ca2+, while ALG-2 persists in both cytoplasm and nucleus. Co-immunoprecipitation, gel filtration, immunofluorescence, subcellular fractionation The Journal of Biological Chemistry High 11278427
2002 ALG-2 directly interacts with the N-terminal domain of annexin XI (and similarly annexin VII) in a Ca2+-dependent manner; dissociation constants ~70 nM (high affinity) and ~500–700 nM (low affinity) were measured. Yeast two-hybrid, biotin-ALG-2 overlay assay, surface plasmon resonance (SPR) Biochemical and Biophysical Research Communications / Biochimica et Biophysica Acta High 11883939 12445460
2002 ALG-2 interacts with the C-terminus of ASK1 in a Ca2+-dependent and isoform-specific manner (ALG-2,1 does not bind); co-transfection of ALG-2 causes nuclear redistribution of ASK1 and suppresses ASK1-mediated JNK activation. Co-immunoprecipitation, in vitro binding, cotransfection/subcellular localization, JNK reporter assay FEBS Letters Medium 12372597
2002 The fifth EF-hand of ALG-2 (and peflin) is essential for dimerization and protein stability; deletion of EF5 leads to rapid proteasomal degradation of the monomer. Exogenous expression of deletion mutants, pulse-chase, proteasome inhibitor (MG132) rescue, Western blot Archives of Biochemistry and Biophysics Medium 11883899
2003 Human ALG2 (hALG2) is an α1,3-mannosyltransferase that elongates Man1GlcNAc2-PP-dolichol; deficiency causes CDG-Ii with accumulation of Man1 and Man2 LLO intermediates. Expression of wild-type but not mutant hALG2 rescues both patient fibroblasts and yeast alg2-1 cells. Mannosyltransferase activity assay in patient fibroblast extracts, complementation of yeast alg2-1, genetic analysis of patient mutations The Journal of Biological Chemistry High 12684507
2004 ALG-2 interacts with the ESCRT-I component TSG101 directly via its Pro-rich region in a Ca2+-dependent manner; indirect Ca2+-dependent association with hVps28 and hVps37A occurs through TSG101. ALG-2 co-localizes with aberrant endosomes (SKD1 dominant-negative) in a Ca2+-dependent fashion. GST pulldown, yeast two-hybrid, biotin-ALG-2 overlay assay, immunofluorescence with Ca2+ chelator (BAPTA) The Biochemical Journal High 16004603
2004 ALG-2 interacts directly with the Alix C-terminal Pro-rich region (residues 794–827) via four tandem PxY repeats; alanine substitution of critical Pro and Tyr residues ablates binding. ALG-2 is required for the punctate subcellular distribution of Alix. Yeast two-hybrid, biotin-ALG-2 overlay, co-immunoprecipitation, Ca2+-binding-deficient mutant, fluorescence microscopy Journal of Biochemistry High 14999017
2004 Yeast Alg1, Alg2, and Alg11 mannosyltransferases form distinct physical complexes in the ER membrane; Alg1 self-assembles via a C-terminal domain distinct from its Alg2/Alg11 interaction domain; catalytically inactive Alg1 alleles cause dominant-negative phenotypes consistent with functional complex assembly. Co-immunoprecipitation, genetic complementation, dominant-negative analysis in S. cerevisiae Glycobiology High 15044395
2006 ALG-2 is recruited to ER exit sites (ERES) by Ca2+-dependent binding to Sec31A (a COPII outer coat component); ALG-2 in turn stabilizes Sec31A at ERES. Ca2+-binding-deficient ALG-2 (E47A/E114A) fails to localize to ERES and fails to stabilize Sec31A. Co-immunoprecipitation, RNAi, Ca2+ ionophore (A23187) and chelator (BAPTA-AM) treatment, immunofluorescence confocal microscopy, GST pulldown Molecular Biology of the Cell / Biochemical and Biophysical Research Communications High 16957052 17196169
2006 In vitro reconstitution demonstrates that S. cerevisiae Alg2 is a bifunctional enzyme catalyzing sequential α1,3- then α1,6-mannosylation to form the first branched pentasaccharide (Man3GlcNAc2-PP-Dol) intermediate in the dolichol pathway. In vitro mannosyltransferase assay with recombinant Alg2 and defined dolichylpyrophosphate-linked substrates from E. coli overexpression Biochemistry High 16878994
2006 ALG-2 subcellular localization oscillates in synchrony with intracellular Ca2+ oscillations induced by physiological stimuli (ATP, EGF, prostaglandin, histamine); Ca2+-binding-deficient ALG-2 does not redistribute, linking ALG-2 dynamics to Ca2+ signaling. Live-cell imaging of tagged ALG-2 with simultaneous Ca2+ indicator, Ca2+-binding mutant comparison Biochemical and Biophysical Research Communications High 17214967
2006 Nuclear translocation of ALG-2 is induced by the RNA-binding protein RBM22; when co-expressed, ALG-2 translocates to the nucleus where RBM22 is located, indicating RBM22 drives ALG-2 nuclear import. Fluorescent fusion protein co-expression, confocal microscopy in NIH 3T3 cells and zebrafish embryos Biochimica et Biophysica Acta Medium 17045351
2008 Alix and ALG-2 interact with pro-caspase-8 in a Ca2+-dependent manner and form a complex with TNF-R1 on endosomes; deletion of the ALG-2-binding site in Alix significantly reduces TNF-R1-induced cell death without affecting receptor endocytosis. Mass spectrometry of co-immunoprecipitates, co-immunoprecipitation, deletion mutant Alix (ΔAlg-2 binding site), cell death assay The Journal of Biological Chemistry High 18936101
2009 ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101: Alix requires its ALG-2-binding site (not its PSAP-TSG101 binding motif) for Ca2+-dependent pulldown of TSG101; ALG-2 knockdown abolishes the association; the ALG-2 dimer bridges the two binding partners. Strep-tag pulldown assays, ALG-2 knockdown, recombinant ALG-2 add-back, dimerization-defective mutant Biochemical and Biophysical Research Communications High 19520058
2009 ALG-2 directly binds the NH2-terminal cytosolic tail of mucolipin-1 (MCOLN1) in a strictly Ca2+-dependent manner via residues 37–49 of MCOLN1; ALG-2 regulates MCOLN1 function as mutation of the ALG-2-binding domain in MCOLN1 reduces MCOLN1-induced aberrant endosome aggregation. In vitro binding assay, co-localization, mutagenesis of MCOLN1 ALG-2-binding domain The Journal of Biological Chemistry High 19864416
2009 Biochemical characterization of yeast Alg2 establishes it as a bifunctional α1,3- and α1,6-mannosyltransferase in ER LLO biosynthesis; topology analysis shows two N-terminal transmembrane spans anchor it to the ER; Lys230 is essential for catalytic activity while an EX7E motif is dispensable. In vitro mannosyltransferase assay, topology analysis, site-directed mutagenesis (K230, EX7E motif) The Journal of Biological Chemistry High 19282279
2010 Crystal structure of the ALG-2(ΔGF122) isoform explains its inability to bind Alix: deletion of Gly121-Phe122 deforms the main-chain wall facing pockets 1 and 2 and repositions Arg125 to occlude pocket 1, not loss of the F122 side chain per se. F122 substitution with Ala or Gly (not Trp) actually increases Alix binding. X-ray crystallography, pulldown assays with F122 substitution mutants BMC Structural Biology High 20691033
2010 The ALG-2-binding site (ABS, residues 839–851) in Sec31A is necessary and sufficient for direct ALG-2 binding; FRAP analysis reveals that ABS deletion reduces the high-affinity population of Sec31A at ERES, indicating ALG-2 controls Sec31A retention kinetics. Biotin-ALG-2 overlay assay, stable GFP-ALG-2/Sec31A-RFP cell lines, Ca2+ mobilization, FRAP Bioscience, Biotechnology, and Biochemistry High 20834162
2013 ALG-2 attenuates COPII vesicle budding in vitro by binding to the Pro-rich region of Sec31A; this requires an intact EF-hand 1 Ca2+-binding site in ALG-2. ALG-2/Ca2+ increases recruitment of Sec23/24 and Sec13/31A to liposomes and mediates Sec31A-Sec23 bridging. In vitro COPII budding assay, liposome recruitment assay, EF1 mutant ALG-2 PLoS ONE High 24069399
2013 Nuclear ALG-2 interacts with CHERP (Ca2+ homeostasis ER protein) in a Ca2+-dependent manner at nuclear speckles; knockdown of CHERP or ALG-2 alters alternative splicing of IP3R1 pre-mRNA, and CHERP binds IP3R1 RNA. ALG-2 is recruited to CHERP-localizing nuclear speckles upon Ca2+ mobilization. Co-immunoprecipitation, live-cell time-lapse imaging, siRNA knockdown, RNA immunoprecipitation, RT-PCR for splicing isoforms The Journal of Biological Chemistry High 24078636
2013 Mutations in ALG2 cause congenital myasthenic syndrome; the ALG2 p.Val68Gly mutation severely reduces ALG2 protein expression in patient muscle and cell cultures. ALG2 functions as an α1,3-mannosyltransferase in early steps of asparagine-linked glycosylation, critical for proper NMJ function. Linkage analysis, exome/genome sequencing, Western blot of patient tissue and transfected cells, SiRNA knockdown of ALG14 with AChR surface expression readout Brain High 23404334
2013 VPS37B and VPS37C isoforms of ESCRT-I interact more strongly with ALG-2 than TSG101; purified recombinant ESCRT-I/ALIX/ALG-2 can form a ternary complex in vitro in a Ca2+-dependent manner. Far-Western blot with biotin-ALG-2, pulldown with recombinant proteins, in vitro reconstitution Bioscience, Biotechnology, and Biochemistry Medium 23924735
2015 X-ray crystal structure of ALG-2 bound to a Sec31A peptide (type 2 motif, PXPGF) shows binding to a third hydrophobic pocket (Pocket 3), distinct from the Pocket 1/2 used by Alix. F85A mutation abrogates Sec31A binding but not Alix binding; Y180A eliminates Alix binding but not Sec31A binding. X-ray crystallography of ALG-2/Sec31A peptide complex, alanine mutagenesis of pocket residues, pulldown binding assays International Journal of Molecular Sciences High 25667979
2015 Ca2+-dependent ALG-2 interaction with ALIX relieves ALIX intramolecular autoinhibition and promotes CHMP4-dependent ALIX membrane association, thereby enabling ALIX function in MVB sorting of ubiquitinated EGFR specifically (not cytokinesis or EIAV budding). Co-immunoprecipitation, membrane fractionation, EGFR MVB sorting assay, ALIX deletion and CHMP4-binding mutants, siRNA knockdown Cell Discovery High 27462417
2016 ALG-2 promotes ER exit site (ERES) localization and Ca2+-dependent polymerization of TFG protein; ALG-2 overexpression accumulates TFG at ERES; deletion of TFG's ALG-2-binding motif shortens TFG half-life at ERES. Immunostaining, live-cell time-lapse imaging with Ca2+ mobilization, in vitro cross-linking polymerization assay, Co-IP The FEBS Journal High 27813252
2017 ALG-2 interacts Ca2+-dependently with MISSL, and together they regulate ER-to-Golgi transport; knockdown of either ALG-2 or MISSL similarly attenuates SEAP secretion and delays procollagen I ER-to-Golgi transport. ALG-2/MISSL interact with MAP1B, which negatively regulates this secretory pathway. Co-IP, live-cell imaging, siRNA knockdown, secreted alkaline phosphatase (SEAP) secretion assay, procollagen transport assay The Journal of Biological Chemistry High 28864773
2018 MAP1B interacts with ALG-2 Ca2+-dependently via a unique mode (no canonical ABM-1/ABM-2 motif); MAP1B competes with ABM-2-containing proteins such as Sec31A for ALG-2 binding, and MAP1B overexpression disperses ALG-2 and Sec31A from ERES. Co-IP, pulldown with MAP1B mutants, co-localization microscopy, MAP1B knockout cells Biochemical and Biophysical Research Communications Medium 29432744
2018 ALG-2 participates in plasma membrane repair after damage by electroporation or digitonin; ALG-2 KO cells are more sensitive to electroporation, reversible by ALG-2 re-expression; Ca2+-binding-deficient ALG-2 does not protect, and a blocking ALIX peptide abolishes protection. ALG-2 gene knockout (DT-40 cells), electroporation and digitonin survival assays, Ca2+-binding mutant and ALIX-peptide blocking experiments PLoS ONE High 30240438
2020 ALG-2 directly interacts with Rpn3, a component of the 26S proteasome; upon Ca2+ influx following T cell activation, ALG-2 regulates proteasome activity, which controls MCL1 stability and accelerates T cell apoptosis during immune contraction. Co-immunoprecipitation, proteasome activity assay, MCL1 stability assay, ALG-2 knockdown in T cells Cell Death & Disease Medium 31919392
2020 ALG-2 interacts with SARAF (a negative regulator of SOCE) Ca2+-dependently; ALG-2 overexpression interferes with SARAF ubiquitination, stabilizing SARAF, and promotes Ca2+-dependent SARAF dimerization through its ABM-2 motif. Pulldown assay, co-IP, ubiquitination assay, half-life analysis, site-directed mutagenesis of ABM-2 International Journal of Molecular Sciences Medium 32878247
2020 ALG-2 interacts with FasL (FASLG) and regulates its intracellular vesicle-mediated transport, thereby influencing T cell apoptosis via the FasL–Fas pathway. Co-immunoprecipitation, subcellular localization microscopy, ALG-2 knockdown with FasL trafficking readout The Biochemical Journal Medium 32766719
2021 ALG-2 suppresses STING-mediated type I interferon signaling by associating with the C-terminal tail of STING and inhibiting its trafficking from the ER to perinuclear vesicles; this requires intact Ca2+-coordinating residues in ALG-2; ALG-2 knockout increases IFN expression upon HSV-1 or cGAMP stimulation. ALG-2 knockout (THP-1 cells), co-immunoprecipitation, immunofluorescence trafficking assay, Ca2+-binding mutant ALG-2 Journal of Cell Science High 34787301
2021 CDIP1 interacts with ALG-2 in a Ca2+-dependent manner; ALG-2 promotes CDIP1 association with ESCRT-I (specifically VPS37B/C-containing complexes); co-expression of ALG-2 and ESCRT-I enhances CDIP1-induced caspase-3/7 cell death. Co-immunoprecipitation, caspase-3/7 activity assay, ALG-2 and ESCRT-I co-expression experiments International Journal of Molecular Sciences Medium 33503978
2021 ALG-2 and peflin form a hetero-bifunctional COPII regulator; at steady-state Ca2+, ALG-2/peflin heterocomplexes bind ERES and buffer secretion; Ca2+ signaling shifts balance toward peflin-lacking ALG-2 complexes that stimulate secretion; ALG-2-dependent effects on secretion can be opposing depending on signal intensity and cell type. Live-cell imaging, siRNA knockdown, secretion assays (SEAP, collagen I), ERES fractionation, Ca2+ agonist treatments in NRK and PC12 cells The Journal of Biological Chemistry High 34762908
2022 Oxidative stress-induced Ca2+ flux triggers JIP4 phosphorylation at T217 by CaMK2G, which activates a JIP4–TRPML1–ALG-2 pathway that promotes lysosomal retrograde transport (clustering near MTOC) and autophagy as a protective response. Knockout cells, phospho-specific mutants, lysosomal positioning assay, Ca2+ flux measurement, CaMK2G kinase assay The EMBO Journal Medium 36394115
2022 Human ALG2 prefers to transfer α1,3-mannose before α1,6-mannose onto M1GlcNAc2-PP-Dol under physiological conditions, but excess GDP-Man donor or elevated M1Gn2 substrate can shift it toward first producing the M2Gn2(α1,6) intermediate; single membrane-binding domain anchors hAlg2 to ER (differs from yeast 4-domain topology). LC-MS quantitative kinetics assay with purified hAlg2, topology analysis, defined LLO substrates Communications Biology High 35136180
2024 Ca2+-dependent direct membrane binding by ALG-2 is mediated by electrostatic and hydrophobic interactions; charge-reversed ALG-2 mutants reduce ERES localization after thapsigargin-induced Ca2+ release but still localize to lysosomes (rescued by ESCRT-I binding); direct membrane binding and protein binding are mechanistically distinct pathways. GUV-based membrane binding experiments, molecular dynamics simulations, charge-reversal mutagenesis, in vitro reconstitution with ESCRT-I, live-cell ERES localization Proceedings of the National Academy of Sciences of the USA High 38386713
2024 ALG-2, upon lysosomal Ca2+ release, recruits ESCRT proteins to lysosomes and enhances lysosomal membrane resilience to osmotic stress; the ΔGF122 splice variant of ALG-2 that cannot bind ESCRTs does not confer this protection; activating TRPML1 without membrane damage is sufficient to recruit ALG-2/ESCRTs and protect lysosomes. Lysosomal leakage/rupture assays, Ca2+ chelation (BAPTA), ΔGF122 ALG-2 mutant, TRPML1 activation, immunofluorescence redistribution assay Proceedings of the National Academy of Sciences of the USA High 38352356 38781205
2024 ERESs undergo lysosome-dependent microautophagy triggered by nutrient stress (mTOR inhibition, amino acid starvation); this requires ubiquitinated SEC31, ALG-2, and ALIX; ALG-2 knockout or function-blocking ALIX mutations prevent ERES engulfment by lysosomes; the pathway was reconstituted in vitro with purified components on lysosomal lipid-mimicking GUVs. Super-resolution live-cell imaging, FIB-SEM, ALG-2 knockout, ALIX function-blocking mutants, in vitro GUV reconstitution Developmental Cell High 38593803

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Interfering with apoptosis: Ca(2+)-binding protein ALG-2 and Alzheimer's disease gene ALG-3. Science (New York, N.Y.) 450 8560270
1999 Alix, a novel mouse protein undergoing calcium-dependent interaction with the apoptosis-linked-gene 2 (ALG-2) protein. Cell death and differentiation 214 10200558
1999 Cloning of AIP1, a novel protein that associates with the apoptosis-linked gene ALG-2 in a Ca2+-dependent reaction. The Journal of biological chemistry 201 9880530
2000 The glioma-associated protein SETA interacts with AIP1/Alix and ALG-2 and modulates apoptosis in astrocytes. The Journal of biological chemistry 111 10858458
2013 Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. Brain : a journal of neurology 107 23404334
2003 A new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharide biosynthesis. The Journal of biological chemistry 94 12684507
2006 The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum exit sites by Sec31A and stabilizes the localization of Sec31A. Molecular biology of the cell 86 16957052
2009 Identification of the penta-EF-hand protein ALG-2 as a Ca2+-dependent interactor of mucolipin-1. The Journal of biological chemistry 79 19864416
2006 ALG-2 directly binds Sec31A and localizes at endoplasmic reticulum exit sites in a Ca2+-dependent manner. Biochemical and biophysical research communications 76 17196169
2001 Structure of apoptosis-linked protein ALG-2: insights into Ca2+-induced changes in penta-EF-hand proteins. Structure (London, England : 1993) 74 11525164
2001 Peflin and ALG-2, members of the penta-EF-hand protein family, form a heterodimer that dissociates in a Ca2+-dependent manner. The Journal of biological chemistry 71 11278427
1999 Apoptosis-linked gene product ALG-2 is a new member of the calpain small subunit subfamily of Ca2+-binding proteins. Biochemistry 71 10360947
2007 Congenital Disorders of Glycosylation: CDG-I, CDG-II, and beyond. Current molecular medicine 69 17584079
2003 Up-regulation of ALG-2 in hepatomas and lung cancer tissue. The American journal of pathology 69 12819013
2005 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. The Biochemical journal 68 16004603
2013 MAN1B1 deficiency: an unexpected CDG-II. PLoS genetics 64 24348268
2002 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. Biochimica et biophysica acta 64 12445460
2012 Developmental characterization of the microRNA-specific C. elegans Argonautes alg-1 and alg-2. PloS one 62 22448270
2004 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. Journal of biochemistry 62 14999017
2002 ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca(2+)-dependent manner. Biochemical and biophysical research communications 60 11883939
2004 Physical interactions between the Alg1, Alg2, and Alg11 mannosyltransferases of the endoplasmic reticulum. Glycobiology 59 15044395
2011 Structure and function of ALG-2, a penta-EF-hand calcium-dependent adaptor protein. Science China. Life sciences 56 21786200
2008 Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death. The Journal of biological chemistry 56 18936101
2006 Do Alix and ALG-2 really control endosomes for better or for worse? Biology of the cell 56 16354163
1998 Calcium-induced exposure of a hydrophobic surface of mouse ALG-2, which is a member of the penta-EF-hand protein family. Journal of biochemistry 55 9832622
2006 In vitro evidence for the dual function of Alg2 and Alg11: essential mannosyltransferases in N-linked glycoprotein biosynthesis. Biochemistry 54 16878994
2000 Two forms of the apoptosis-linked protein ALG-2 with different Ca(2+) affinities and target recognition. The Journal of biological chemistry 50 10744743
2016 Multifaceted Roles of ALG-2 in Ca(2+)-Regulated Membrane Trafficking. International journal of molecular sciences 49 27571067
2002 ALG-2: a Ca2+ -binding modulator protein involved in cell proliferation and in cell death. Biochimica et biophysica acta 49 12445461
2009 Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101. Biochemical and biophysical research communications 47 19520058
1993 Biosynthesis of asparagine-linked oligosaccharides in Saccharomyces cerevisiae: the alg2 mutation. Glycobiology 47 8400550
1997 Dissociation of apoptosis and activation of IL-1beta-converting enzyme/Ced-3 proteases by ALG-2 and the truncated Alzheimer's gene ALG-3. Journal of immunology (Baltimore, Md. : 1950) 46 9164928
2007 The apoptosis linked gene ALG-2 is dysregulated in tumors of various origin and contributes to cancer cell viability. Molecular oncology 43 19383317
2013 ALG-2 attenuates COPII budding in vitro and stabilizes the Sec23/Sec31A complex. PloS one 41 24069399
2016 TMEM165 deficiencies in Congenital Disorders of Glycosylation type II (CDG-II): Clues and evidences for roles of the protein in Golgi functions and ion homeostasis. Tissue & cell 40 27401145
2013 Impact of disease-causing mutations on TMEM165 subcellular localization, a recently identified protein involved in CDG-II. Human molecular genetics 40 23575229
2006 POSH, a scaffold protein for JNK signaling, binds to ALG-2 and ALIX in Drosophila. FEBS letters 38 16698022
2006 ALG-2 oscillates in subcellular localization, unitemporally with calcium oscillations. Biochemical and biophysical research communications 37 17214967
2010 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. Bioscience, biotechnology, and biochemistry 36 20834162
2006 Nuclear translocation of the calcium-binding protein ALG-2 induced by the RNA-binding protein RBM22. Biochimica et biophysica acta 35 17045351
2016 ALG-2 interacting protein-X (Alix) is essential for clathrin-independent endocytosis and signaling. Scientific reports 34 27244115
2015 ALG-2 activates the MVB sorting function of ALIX through relieving its intramolecular interaction. Cell discovery 34 27462417
2004 ALG-2, a multifunctional calcium binding protein? Frontiers in bioscience : a journal and virtual library 34 14977589
1999 Peflin, a novel member of the five-EF-hand-protein family, is similar to the apoptosis-linked gene 2 (ALG-2) protein but possesses nonapeptide repeats in the N-terminal hydrophobic region. Biochemical and biophysical research communications 34 10486255
2008 ALG-2 knockdown in HeLa cells results in G2/M cell cycle phase accumulation and cell death. Biochemical and biophysical research communications 33 19013425
2002 Interaction of ALG-2 with ASK1 influences ASK1 localization and subsequent JNK activation. FEBS letters 33 12372597
2016 The calcium-binding protein ALG-2 promotes endoplasmic reticulum exit site localization and polymerization of Trk-fused gene (TFG) protein. The FEBS journal 32 27813252
2024 Ca2+-sensor ALG-2 engages ESCRTs to enhance lysosomal membrane resilience to osmotic stress. Proceedings of the National Academy of Sciences of the United States of America 31 38781205
2006 The Caenorhabditis elegans Argonautes ALG-1 and ALG-2: almost identical yet different. Cold Spring Harbor symposia on quantitative biology 31 17381296
2015 Structural analysis of the complex between penta-EF-hand ALG-2 protein and Sec31A peptide reveals a novel target recognition mechanism of ALG-2. International journal of molecular sciences 30 25667979
2017 Chemo-enzymatic synthesis of lipid-linked GlcNAc2Man5 oligosaccharides using recombinant Alg1, Alg2 and Alg11 proteins. Glycobiology 29 28575298
2003 Properties of the co-chaperone protein p23 erroneously attributed to ALG-2 (apoptosis-linked gene 2). FEBS letters 29 14675759
2013 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. The Journal of biological chemistry 28 24078636
2009 Biochemical characterization and membrane topology of Alg2 from Saccharomyces cerevisiae as a bifunctional alpha1,3- and 1,6-mannosyltransferase involved in lipid-linked oligosaccharide biosynthesis. The Journal of biological chemistry 27 19282279
2013 VPS37 isoforms differentially modulate the ternary complex formation of ALIX, ALG-2, and ESCRT-I. Bioscience, biotechnology, and biochemistry 26 23924735
2002 Both ALG-2 and peflin, penta-EF-hand (PEF) proteins, are stabilized by dimerization through their fifth EF-hand regions. Archives of biochemistry and biophysics 26 11883899
2009 Alix and ALG-2 make a link between endosomes and neuronal death. Biochemical Society transactions 24 19143631
2007 The calcium binding protein ALG-2 binds and stabilizes Scotin, a p53-inducible gene product localized at the endoplasmic reticulum membrane. Archives of biochemistry and biophysics 22 17889823
2000 Increased expression of apoptosis-linked gene 2 (ALG2) in the rat brain after temporary focal cerebral ischemia. Neuroscience 22 10683420
2022 Oxidative stress-induced phosphorylation of JIP4 regulates lysosomal positioning in coordination with TRPML1 and ALG2. The EMBO journal 21 36394115
2017 The calcium-binding protein ALG-2 regulates protein secretion and trafficking via interactions with MISSL and MAP1B proteins. The Journal of biological chemistry 21 28864773
2024 COPII with ALG2 and ESCRTs control lysosome-dependent microautophagy of ER exit sites. Developmental cell 19 38593803
2017 ALG2 regulates glioblastoma cell proliferation, migration and tumorigenicity. Biochemical and biophysical research communications 18 28300556
2024 Mechanism and cellular function of direct membrane binding by the ESCRT and ERES-associated Ca2+-sensor ALG-2. Proceedings of the National Academy of Sciences of the United States of America 16 38386713
2021 The Novel ALG-2 Target Protein CDIP1 Promotes Cell Death by Interacting with ESCRT-I and VAPA/B. International journal of molecular sciences 15 33503978
2021 Development and Initial Characterization of Cellular Models for COG Complex-Related CDG-II Diseases. Frontiers in genetics 15 34603392
2020 ALG-2 couples T cell activation and apoptosis by regulating proteasome activity and influencing MCL1 stability. Cell death & disease 15 31919392
2010 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 structural biology 15 20691033
2021 ALG-2 and peflin regulate COPII targeting and secretion in response to calcium signaling. The Journal of biological chemistry 14 34762908
1998 Characterization of alg2 encoding a mannosyltransferase in the zygomycete fungus Rhizomucor pusillus. Gene 13 9795208
2010 Stress induced subcellular distribution of ALG-2, RBM22 and hSlu7. Biochimica et biophysica acta 12 21122810
2008 ALG-2 interacting protein AIP1: a novel link between D1 and D3 signalling. The European journal of neuroscience 12 18380665
2022 ALG2 inhibits the epithelial-to-mesenchymal transition and stemness of ovarian granulosa cells through the Wnt/β-catenin signaling pathway in polycystic ovary syndrome. Reproductive biology 11 36327672
2009 The mechanism of Ca2+-dependent recognition of Alix by ALG-2: insights from X-ray crystal structures. Biochemical Society transactions 11 19143629
2021 ALG2 regulates type I interferon responses by inhibiting STING trafficking. Journal of cell science 10 34787301
2018 ALG-2 participates in recovery of cells after plasma membrane damage by electroporation and digitonin treatment. PloS one 10 30240438
2020 The Penta-EF-Hand ALG-2 Protein Interacts with the Cytosolic Domain of the SOCE Regulator SARAF and Interferes with Ubiquitination. International journal of molecular sciences 9 32878247
2013 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+. Bioscience, biotechnology, and biochemistry 9 23649269
2021 The Argonaute Proteins ALG-1 and ALG-2 Are Linked to Stress Resistance and Proteostasis. microPublication biology 8 34723149
2021 Novel pathogenic ALG2 mutation causing congenital myasthenic syndrome: A case report. Neuromuscular disorders : NMD 8 34980536
2020 ALG2 Influences T cell apoptosis by regulating FASLG intracellular transportation. The Biochemical journal 8 32766719
2019 Structures and functions of penta-EF-hand calcium-binding proteins and their interacting partners: enigmatic relationships between ALG-2 and calpain-7. Bioscience, biotechnology, and biochemistry 8 31814542
2018 A microtubule-associated protein MAP1B binds to and regulates localization of a calcium-binding protein ALG-2. Biochemical and biophysical research communications 8 29432744
2018 Adaptor functions of the Ca2+-binding protein ALG-2 in protein transport from the endoplasmic reticulum. Bioscience, biotechnology, and biochemistry 8 30259798
2012 Prediction of a new ligand-binding site for type 2 motif based on the crystal structure of ALG-2 by dry and wet approaches. International journal of molecular sciences 8 22837710
2021 Mass spectrometry glycophenotype characterization of ALG2-CDG in Argentinean patients with a new genetic variant in homozygosis. Glycoconjugate journal 7 33644825
2013 Biochemical and immunological detection of physical interactions between penta-EF-hand protein ALG-2 and its binding partners. Methods in molecular biology (Clifton, N.J.) 7 23296612
2001 Mapping of the interaction sites between apoptosis linked gene ALG-2 and HEED. Molecules and cells 7 11804327
1999 Characterization of an alg2 mutant of the zygomycete fungus Rhizomucor pusillus. Glycobiology 7 10561453
2022 Topological and enzymatic analysis of human Alg2 mannosyltransferase reveals its role in lipid-linked oligosaccharide biosynthetic pathway. Communications biology 6 35136180
2021 A patient-based medaka alg2 mutant as a model for hypo-N-glycosylation. Development (Cambridge, England) 6 34106226
2003 ALG2, the Hansenula polymorpha isocitrate lyase gene. Yeast (Chichester, England) 6 12845606
2018 Thermodynamic Characterization of the Ca2+-Dependent Interaction Between SOUL and ALG-2. International journal of molecular sciences 5 30501057
2022 An Autographa californica nucleopolyhedrovirus-encoded microRNA, AcMNPV-miR-4, downregulates the expression of host gene alg-2. The Journal of general virology 3 35830328
2008 Crystallization and X-ray diffraction analysis of N-terminally truncated human ALG-2. Acta crystallographica. Section F, Structural biology and crystallization communications 3 18997320
2001 Crystallization and preliminary crystallographic studies of an apoptosis-linked calcium-binding protein ALG-2. Acta crystallographica. Section D, Biological crystallography 3 11468406
1998 Localization of mRNA for the apoptosis-linked gene ALG-2 in young and aged rat brain. Neuroreport 3 9674578
2024 Ca 2+ -sensor ALG-2 engages ESCRTs to enhance lysosomal membrane resilience to osmotic stress. bioRxiv : the preprint server for biology 2 38352356
2018 Ligation events influence ALG-2 dimerization. Biophysical chemistry 2 29758467
2010 Simultaneous targeting of Requiem & Alg-2 in Chinese hamster ovary cells for improved recombinant protein production. Molecular biotechnology 2 20571937