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Showing PDCD6 — ALG-2 is a alias.

PDCD6

Programmed cell death protein 6 · UniProt O75340

Length
191 aa
Mass
21.9 kDa
Annotated
2026-06-10
100 papers in source corpus 53 papers cited in narrative 51 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDCD6/ALG-2 is a penta-EF-hand Ca2+-binding protein that functions as a Ca2+-sensing molecular adaptor coupling intracellular Ca2+ transients to membrane traffic, membrane repair, and cell-fate decisions (PMID:8560270, PMID:11525164). Ca2+ binding at its high-affinity EF-hands triggers a conformational change that exposes a hydrophobic surface (PMID:9832622, PMID:10360947), and crystallographic work resolved this as an arginine-switch in which Ca2+ loading at EF3 repositions Arg125 to open hydrophobic pockets that capture Pro-rich peptide motifs in partner proteins (PMID:18940611); distinct pockets recognize type 1 (PPYP, as in ALIX/TSG101) versus type 2 (PXPGF, as in Sec31A) motifs, and the alternatively spliced ALG-2(ΔGF122) isoform reshapes these pockets to alter target selectivity (PMID:18256029, PMID:20691033, PMID:25667979). Functional ALG-2 acts as a homodimer (mediated by the fifth EF-hand) and additionally binds acidic membranes Ca2+-dependently, with membrane and peptide engagement acting together for recruitment (PMID:10360947, PMID:38386713). As an adaptor it bridges ALIX and ESCRT-I, relieves ALIX autoinhibition to promote CHMP4-dependent membrane association, and thereby drives MVB sorting of activated EGFR and recruits ESCRT to reinforce lysosomal membranes against rupture (PMID:19520058, PMID:27462417, PMID:38781205). At ER exit sites ALG-2 binds and stabilizes the COPII outer-coat protein Sec31A and, together with its paralog peflin, constitutes a hetero-bifunctional Ca2+-tunable regulator of ER-to-Golgi secretion, also polymerizing TFG and recruiting MISSL/MAP1B (PMID:16957052, PMID:17196169, PMID:25006245, PMID:27813252, PMID:28864773, PMID:34762908). In the nucleus ALG-2 partners with CHERP to regulate alternative splicing of IP3R1 pre-mRNA (PMID:24078636). ALG-2 was originally identified as a required mediator of Ca2+-regulated apoptosis acting downstream of caspase activation (PMID:8560270, PMID:9164928), and it further couples Ca2+ signals to protein turnover and metabolism by engaging the proteasome subunit Rpn3 to control MCL1 during T-cell contraction and by restraining LDHA-driven lactate production that governs RUBCN lactylation and LC3-associated phagocytosis (PMID:31919392, PMID:39578445).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1996 High

    Established that ALG-2 is a required component of Ca2+-regulated programmed cell death, defining the gene's founding biological role.

    Evidence Death-trap functional selection and antisense depletion in T cell hybridoma cells across TCR, Fas, and glucocorticoid death stimuli

    PMID:8560270

    Open questions at the time
    • Molecular mechanism by which ALG-2 enables death not defined
    • No direct partners identified at this stage
  2. 1997 High

    Placed ALG-2 at a post-caspase step in apoptosis, distinguishing its function from upstream protease activation.

    Evidence Caspase activity and PARP cleavage assays in ALG-2-depleted clones showing normal cleavage yet death protection

    PMID:9164928

    Open questions at the time
    • The downstream effectors ALG-2 acts through were not identified
    • Did not link the apoptotic role to a biochemical activity
  3. 1999 High

    Defined the Ca2+-dependent conformational logic and dimerization of ALG-2, showing Ca2+ binding exposes a hydrophobic surface and EF5 drives homodimerization.

    Evidence TNS fluorescence, gel filtration, cross-linking, CD and EF-hand mutagenesis on recombinant protein

    PMID:10360947 PMID:9832622

    Open questions at the time
    • No physiological binding partner mapped to the exposed surface yet
    • Cellular consequence of the conformational change unresolved
  4. 1999 High

    Identified ALIX/AIP1 as the first strictly Ca2+-dependent ALG-2 partner cooperating in cell death, linking the conformational switch to a functional interaction.

    Evidence Yeast two-hybrid, reciprocal Co-IP, co-localization, and overexpression rescue, confirmed by a parallel study

    PMID:10200558 PMID:9880530

    Open questions at the time
    • Structural basis of the interaction not yet resolved
    • Direct molecular role of the ALG-2-ALIX complex undefined
  5. 2002 High

    Generalized ALG-2 target recognition to a Pro/Gly/Tyr-rich binding mode by reconstituting direct nanomolar Ca2+-dependent binding to annexin VII/XI N-termini.

    Evidence SPR kinetics, GST pull-down, and biotin-ALG-2 overlay with recombinant annexins

    PMID:11883939 PMID:12445460

    Open questions at the time
    • Functional outcome of annexin binding in cells not established
    • Did not yet define the precise peptide motif consensus
  6. 2001 High

    Resolved the first Ca2+-loaded ALG-2 crystal structure, showing a hinge rotation at EF3 that exposes a peptide-accepting cleft at the dimer interface.

    Evidence X-ray crystallography at 2.3 Å of Ca2+-bound ALG-2

    PMID:11525164

    Open questions at the time
    • Did not capture a bound target peptide
    • Residue-level switch mechanism not yet defined
  7. 2005 High

    Extended ALG-2 into the ESCRT machinery by showing direct Ca2+-dependent binding to TSG101 and Ca2+-dependent endosomal recruitment.

    Evidence GST pull-down, yeast two-hybrid, overlay, and immunofluorescence with BAPTA-AM chelation in cells

    PMID:16004603

    Open questions at the time
    • Whether ALG-2 bridges ALIX and ESCRT-I not yet tested
    • Functional consequence for endosomal sorting undefined
  8. 2006 High

    Connected ALG-2 to the early secretory pathway by demonstrating Ca2+-dependent recruitment to ER exit sites via Sec31A and reciprocal stabilization of Sec31A.

    Evidence Ca2+-dependent pull-down, overlay, RNAi, confocal imaging and pharmacological Ca2+ manipulation, independently replicated

    PMID:16957052 PMID:17196169

    Open questions at the time
    • Effect on actual cargo transport rates not yet measured
    • Distinct binding mode versus ALIX/TSG101 not yet resolved
  9. 2006 Medium

    Placed ALG-2 in the nucleus through RBM22-mediated import, hinting at a role beyond membrane traffic.

    Evidence Yeast two-hybrid and confocal co-localization in NIH 3T3 cells and zebrafish embryos

    PMID:17045351

    Open questions at the time
    • No direct binding reconstitution
    • Nuclear function not established at this stage
  10. 2008 High

    Defined the residue-level arginine-switch mechanism, showing Ca2+/EF3 repositions Arg125 to open the primary hydrophobic pocket that captures the ALIX PPYP motif.

    Evidence Multiple crystal structures including the ALG-2/Alix peptide complex plus mutagenesis-validated binding

    PMID:18940611

    Open questions at the time
    • Did not resolve type 2 motif recognition
    • Membrane contribution to recruitment not addressed
  11. 2008 High

    Resolved a second, distinct ALG-2 binding pocket and motif class, explaining how the protein discriminates type 1 (PPYP) from type 2 (PXPGF) ligands.

    Evidence SPR, overlay, GST pull-down and mutagenesis on PLSCR3 ABS-1/ABS-2 sites

    PMID:18256029

    Open questions at the time
    • Cellular role of PLSCR3 binding undefined
    • Structural detail of the second pocket awaited a co-crystal
  12. 2009 High

    Established ALG-2 as a Ca2+-dependent dimeric adaptor that physically bridges ALIX and TSG101, unifying its ESCRT-associated functions.

    Evidence Knockdown plus recombinant add-back ternary-complex reconstitution with isoform and dimerization mutant controls

    PMID:19520058

    Open questions at the time
    • Membrane context of bridging not addressed
    • Downstream sorting cargo not yet defined in this study
  13. 2010 High

    Resolved the structural basis of isoform-selective target recognition, showing ΔGF122 repositions Arg125 to block Pocket 1 and differentially affect partner binding.

    Evidence Crystal structure of ALG-2(ΔGF122) plus systematic mutant binding assays against Alix/TSG101/annexin A11

    PMID:20691033

    Open questions at the time
    • Physiological role of isoform switching not established
    • Did not capture the type 2 pocket structurally
  14. 2014 High

    Demonstrated that ALG-2/Sec31A engagement functionally controls ER-to-Golgi transport and cargo receptor stability, not merely Sec31A localization.

    Evidence Intact-cell transport assays, EM, Ca2+ depletion, and binding-domain disruption with p24/p115 analysis

    PMID:24069399 PMID:25006245

    Open questions at the time
    • Direction of regulation (stimulatory vs inhibitory) not fully reconciled
    • Role of peflin not yet integrated
  15. 2013 High

    Assigned ALG-2 a nuclear function in alternative splicing, linking Ca2+ signaling to IP3R1 pre-mRNA processing via CHERP.

    Evidence Co-IP, live imaging, RNA-IP, and siRNA knockdown with RT-PCR splicing analysis

    PMID:24078636

    Open questions at the time
    • Breadth of ALG-2-dependent splicing targets unknown
    • Mechanism of ALG-2 within the spliceosome undefined
  16. 2015 High

    Resolved the third hydrophobic pocket recognizing the Sec31A type 2 PXPGF motif and validated pocket-specific mutations separating Sec31A from Alix binding.

    Evidence Crystallography of the ALG-2/Sec31A peptide complex plus single-residue substitution binding assays

    PMID:25667979

    Open questions at the time
    • In vivo significance of pocket separation not tested
    • Did not address membrane-binding contribution
  17. 2016 High

    Established that ALG-2 functions selectively as a homodimer at ERES to polymerize TFG and recruit MISSL/MAP1B, expanding its ERES regulatory repertoire.

    Evidence Co-IP, live imaging, in vitro polymerization assays, and double-knockdown epistasis with secretion readouts

    PMID:27813252 PMID:28864773 PMID:29432744

    Open questions at the time
    • How homodimer vs heterodimer selection is regulated in cells unclear
    • Competition between MAP1B and Sec31A binding not fully mapped physiologically
  18. 2016 High

    Defined the molecular consequence of ALG-2-ALIX binding as relief of ALIX autoinhibition driving pathway-specific MVB sorting of activated EGFR.

    Evidence Pull-down, membrane fractionation, EGFR MVB sorting, and dominant-negative ALIX assays distinguishing pathway specificity

    PMID:27462417

    Open questions at the time
    • Why ALG-2 affects MVB sorting but not abscission/budding not fully explained
    • In vivo relevance not established
  19. 2020 Medium

    Linked ALG-2 to regulated protein turnover by showing direct Rpn3/proteasome engagement that controls MCL1 stability during T-cell contraction.

    Evidence Co-IP, proteasome activity assays, and MCL1 stability with T-cell activation/apoptosis readouts

    PMID:31919392

    Open questions at the time
    • Whether Rpn3 binding is direct via the canonical pockets unresolved
    • Reciprocal validation of proteasome regulation limited to single lab
  20. 2021 High

    Integrated ALG-2 with peflin into a hetero-bifunctional COPII regulator that bidirectionally tunes ER export according to Ca2+ signal intensity.

    Evidence ER-to-Golgi transport assays in two cell types with COPII fractionation and ALG-2/peflin knockdowns

    PMID:34762908

    Open questions at the time
    • Quantitative threshold setting between buffering and stimulation undefined
    • Structural basis of heterodimer COPII effect not resolved
  21. 2024 High

    Demonstrated that ALG-2 directly engages acidic membranes Ca2+-dependently and that membrane binding and ESCRT-I binding act together for compartment-specific recruitment.

    Evidence GUV binding, molecular dynamics, charge-reversal mutagenesis, and cellular imaging with in vitro ESCRT-I reconstitution

    PMID:38386713

    Open questions at the time
    • Relative contribution of membrane vs peptide binding across partners not quantified
    • Lipid specificity determinants only partly defined
  22. 2024 High

    Assigned ALG-2 a protective role in lysosomal membrane repair via Ca2+-triggered ESCRT recruitment, with the ESCRT-binding-defective ΔGF122 isoform unable to confer protection.

    Evidence Lysosomal rupture reporters, Ca2+ chelation, GPN/TRPML1 agonists, and isoform-controlled ESCRT recruitment imaging

    PMID:38781205

    Open questions at the time
    • In vivo physiological setting of lysosomal repair not tested
    • Crosstalk with plasma-membrane repair function not delineated
  23. 2024 High

    Connected PDCD6 to immunometabolism by showing it restrains LDHA-driven lactate production, controlling RUBCN lactylation and LC3-associated phagocytosis.

    Evidence Co-IP, knockout mice/macrophages, LDHA inhibition, lactylation site mapping, and bactericidal LAP assays

    PMID:39578445

    Open questions at the time
    • Whether PDCD6-LDHA binding uses the canonical Ca2+/peptide mechanism unclear
    • Ca2+ dependence of this metabolic axis not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse ALG-2 functions—secretory traffic, ESCRT-dependent membrane repair, nuclear splicing, proteasome and metabolic regulation—are coordinated and prioritized by distinct Ca2+ signal patterns within a single cell remains unresolved.
  • No integrated model of partner selection under physiological Ca2+ dynamics
  • In vivo phenotypes tying the molecular activities to organismal physiology largely lacking
  • Mechanistic basis for several Co-IP-only partners (c-Raf, VEGFR-2, DAPk1, PATL1) not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140299 molecular sensor activity 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 1
Localization
GO:0005634 nucleus 3 GO:0005783 endoplasmic reticulum 3 GO:0005764 lysosome 2 GO:0005768 endosome 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-8953854 Metabolism of RNA 1
Partners
ANXA11CHERPPDCD6IP/ALIXPEF1PSMD3SEC31ATFGTSG101
Complex memberships
ALG-2 homodimerALG-2/peflin heterodimerCOPII outer coat (Sec13/31A)ESCRT-I/ALIX/ALG-2 ternary complex

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 ALG-2 (PDCD6) encodes a Ca2+-binding protein required for T cell receptor-, Fas-, and glucocorticoid-induced apoptosis; ALG-2-depleted 3DO T cell hybridoma cells are protected from these death stimuli, placing ALG-2 as a required mediator of Ca2+-regulated apoptotic signaling. Functional selection (death trap assay), antisense depletion of ALG-2 with loss-of-function apoptosis phenotype Science High 8560270
1997 ALG-2 functions downstream of or independently of ICE/Ced-3 (caspase) activation during apoptosis; ALG-2-depleted cells exhibit normal caspase-mediated PARP cleavage yet are protected from cell death, indicating ALG-2 acts at a post-caspase step. Caspase activity assay (fluorogenic substrate, PARP cleavage) in ALG-2-depleted T cell hybridoma clones Journal of Immunology High 9164928
1998 Ca2+ binding to ALG-2 induces exposure of a hydrophobic surface on the protein, as detected by a fluorescent hydrophobicity probe (TNS); this conformational change occurs with half-maximal effect at ~6 µM Ca2+, and Mg2+ is not effective. Fluorescence spectroscopy with hydrophobicity probe TNS; gel filtration; biochemical fractionation of mammalian cells Journal of Biochemistry Medium 9832622
1999 ALG-2 interacts with AIP1/Alix in a strictly Ca2+-dependent manner; both proteins co-localize in the cytosol; overexpression of a truncated AIP1 protects cells from trophic factor withdrawal-induced death, indicating AIP1 cooperates with ALG-2 in the Ca2+-dependent cell death pathway. Yeast two-hybrid screening, co-immunoprecipitation, subcellular co-localization, overexpression rescue assay The Journal of Biological Chemistry High 10200558 9880530
1999 ALG-2 possesses two high-affinity Ca2+-binding sites; Ca2+ binding induces conformational changes in both N- and C-terminal domains; the fifth EF-hand participates in homodimerization; Ca2+ binding to both strong sites is required for Ca2+-induced protein aggregation. Recombinant protein expression, gel filtration, chemical cross-linking, fluorescence spectroscopy, circular dichroism, site-directed mutagenesis (Glu47Ala/Glu114Ala) Biochemistry High 10360947
2000 Two alternatively spliced isoforms of ALG-2 exist (ALG-2,5 full-length and ALG-2,1 lacking Gly121/Phe122); they differ in Ca2+ affinity; ALG-2,1 does not interact with AIP1/Alix despite otherwise similar properties, indicating these two residues are critical for target recognition. cDNA cloning, Ca2+ binding assays, yeast two-hybrid interaction assay The Journal of Biological Chemistry Medium 10744743
2001 X-ray crystal structure of Ca2+-loaded ALG-2 (des1-20, 2.3 Å) reveals five EF-hands folding into eight α-helices, dimer formation, Ca2+ binding to EF1, EF3, and EF5; a rigid-body rotation of EF1-2 relative to EF4-5 (hinge at EF3) upon Ca2+ loading exposes a hydrophobic patch and a large cleft near the dimer interface that accommodates a Gly/Pro-rich peptide. X-ray crystallography at 2.3 Å resolution; limited proteolysis for crystal preparation Structure High 11525164
2001 ALG-2 forms a Ca2+-independent homodimer and a Ca2+-dependent heterodimer with its closest paralog peflin; peflin dissociates from ALG-2 in the presence of Ca2+; peflin translocates to membrane/cytoskeletal fractions in Ca2+ conditions while ALG-2 is also found in the nucleus. Co-immunoprecipitation with monoclonal anti-peflin antibody, epitope-tag co-IP, gel filtration, immunofluorescence, subcellular fractionation The Journal of Biological Chemistry High 11278427
2002 ALG-2 interacts directly and Ca2+-dependently with the N-terminal domain of annexin XI; KD ~70 nM for the high-affinity site; the Pro/Gly/Tyr/Ala-rich hydrophobic region of annexin XI masks Ca2+-dependently exposed hydrophobic surface of ALG-2. Yeast two-hybrid, GST pull-down, biotin-ALG-2 overlay assay, surface plasmon resonance (SPR), fluorescence probe inhibition Biochemical and Biophysical Research Communications High 11883939
2002 ALG-2 binds directly and Ca2+-dependently to the N-terminal domains of both annexin VII and annexin XI with two binding sites (KD ~40-60 nM high-affinity, ~500-700 nM low-affinity), establishing a common PGAYQ-biased binding mode. Biotin-ALG-2 overlay assay, surface plasmon resonance biosensor with GST-fusion proteins Biochimica et Biophysica Acta High 12445460
2002 The fifth EF-hand (EF-5) of both ALG-2 and peflin is essential for dimerization and protein stability; EF-5 deletion mutants are rapidly degraded by the proteasome. Deletion mutagenesis, pulse-chase experiment, proteasome inhibitor (MG132) treatment, Western blot, subcellular fractionation Archives of Biochemistry and Biophysics Medium 11883899
2002 ALG-2 interacts with ASK1 (apoptosis signal-regulating kinase 1) at its C-terminus (aa 941-1375) in a Ca2+-dependent manner; the ALG-2,1 isoform lacking Gly121/Phe122 does not bind ASK1; co-expression of ALG-2 redirects ASK1 to the nucleus and inhibits ASK1-induced JNK activation. Co-immunoprecipitation in BOSC23 cells, in vitro binding, co-transfection with JNK activity readout, subcellular localization by microscopy FEBS Letters Medium 12372597
2004 ALG-2 interacts directly with Alix through a region (aa 794-827) containing four tandem PxY repeats; seven proline and four tyrosine residues in PxY repeats are critical for binding affinity; Ca2+-binding-deficient ALG-2(E47A/E114A) does not co-immunoprecipitate with Alix; ALG-2 is required for the subcellular punctate distribution of the Alix C-terminal half. Yeast two-hybrid, biotin-ALG-2 overlay, alanine-substitution mutagenesis, co-immunoprecipitation, GFP-fusion fluorescence microscopy Journal of Biochemistry High 14999017
2005 ALG-2 directly binds the proline-rich region (PRR) of TSG101 (ESCRT-I component) in a Ca2+-dependent manner; ALG-2 also associates with hVps28 and hVps37A indirectly via TSG101; ALG-2 co-localizes with SKD1(E235Q)-induced aberrant endosomes in a Ca2+-dependent manner; Ca2+ chelation abolishes this punctate endosomal localization. GST pull-down, yeast two-hybrid, biotin-ALG-2 overlay assay, immunofluorescence microscopy, Ca2+ chelator (BAPTA-AM) treatment The Biochemical Journal High 16004603
2006 ALG-2 is recruited to ER exit sites (ERES) via Ca2+-dependent interaction with Sec31A (COPII outer coat component); ALG-2 in turn stabilizes Sec31A at ERES; Ca2+-binding-deficient ALG-2 mutant loses ERES localization; Ca2+ chelation disperses ALG-2 and reduces membrane-associated Sec31A. Ca2+-dependent GST pull-down, biotin-ALG-2 overlay, immunofluorescence confocal microscopy, RNAi knockdown, Ca2+ ionophore/chelator treatments, overexpression of Sec31A PRR as dominant negative Molecular Biology of the Cell High 16957052 17196169
2006 ALG-2 subcellular distribution oscillates between cytosol and punctate (COPII/Sec31A-positive) localization in phase with intracellular Ca2+ oscillations triggered by physiological stimuli (ATP, EGF, prostaglandin, histamine); a Ca2+-binding-deficient mutant does not redistribute. Live-cell fluorescence imaging of tagged ALG-2 simultaneous with Ca2+ indicators; Ca2+-binding-deficient mutant as control Biochemical and Biophysical Research Communications Medium 17214967
2006 ALG-2 is translocated to the nucleus upon co-expression with the RNA-binding protein RBM22, which shuttles between cytoplasm and nucleus; in zebrafish embryos the two proteins co-localize within the nucleus, suggesting RBM22-mediated nuclear import of ALG-2. Yeast two-hybrid screening, confocal microscopy of fluorescent fusions in NIH 3T3 cells and zebrafish embryos Biochimica et Biophysica Acta Medium 17045351
2006 POSH scaffold protein forms a Ca2+-dependent complex with ALG-2 and ALIX in Drosophila; overexpression of ALG-2 causes roughened/melanized eye phenotypes; co-overexpression with POSH enhances these phenotypes; ALG-2 overexpression induces ectopic JNK activation, suggesting POSH/ALG-2/ALIX function together in JNK pathway regulation. Co-immunoprecipitation in Drosophila cells, genetic overexpression in eye imaginal discs, JNK activity assay FEBS Letters Medium 16698022
2007 ALG-2 binds to Scotin (a p53-inducible ER-membrane protein) in a strictly Ca2+-dependent manner; overexpression of ALG-2 increases Scotin protein levels, indicating ALG-2 stabilizes Scotin. In vitro binding assay (synthesized C-terminal Scotin fragment on immobilized ALG-2), co-immunoprecipitation in MCF7 and U2OS cell lines, overexpression Western blot Archives of Biochemistry and Biophysics Medium 17889823
2008 X-ray crystal structures of Ca2+-free and Ca2+-bound ALG-2 and of the ALG-2/Alix799-814 peptide complex reveal a Ca2+/EF3-driven arginine switch: Ca2+ binding to EF3 repositions Arg125, opening a primary hydrophobic pocket (Pocket 1) that accepts the PPYP motif of Alix; in vitro binding assays with mutant proteins validate this mechanism. X-ray crystallography (multiple structures), in vitro binding assay with ALG-2 and Alix mutants Structure High 18940611
2008 ALG-2 interacts with Alix and pro-caspase-8; Alix forms a complex with TNF-R1-containing endosomes in a manner dependent on ESCRT binding; deletion of the ALG-2-binding site on Alix significantly reduces TNF-R1-induced cell death without affecting receptor endocytosis, placing ALG-2 in the TNF-R1 death signaling pathway. Mass spectrometry of Alix co-immunoprecipitates, Co-IP, overexpression of Alix deletion mutants, cell death assays, motoneuron primary culture The Journal of Biological Chemistry Medium 18936101
2008 ALG-2 interacts with PLSCR3 Ca2+-dependently via two distinct binding sites: ABS-1 (PPYP-type, type 1 motif, Alix-like) recognized only by full-length ALG-2, and ABS-2 (PXPGF-type, type 2 motif) recognized by both full-length ALG-2 and the ALG-2(ΔGF122) isoform; Phe49 in ABS-2 is critical for binding. Co-immunoprecipitation, GST pull-down, biotin-ALG-2 overlay, surface plasmon resonance with synthetic oligopeptides, mutagenesis The Journal of Biological Chemistry High 18256029
2009 ALG-2 functions as a Ca2+-dependent adaptor protein that bridges Alix and TSG101: ALG-2 knockdown abolishes Alix-TSG101 association in pulldown assays; recombinant ALG-2 restores the interaction; the shorter ALG-2(ΔGF122) isoform and a dimerization-defective mutant cannot bridge the two proteins, indicating the ALG-2 dimer is required. Strep-tag pulldown assay with ALG-2 knockdown cells, add-back of purified recombinant ALG-2, isoform and dimerization mutant controls Biochemical and Biophysical Research Communications High 19520058
2009 ALG-2 binds directly to the NH2-terminal cytosolic tail of mucolipin-1 (MCOLN1) Ca2+-dependently; the interaction is mediated by residues 37-49 of MCOLN1; mutation of the ALG-2-binding domain in MCOLN1 reduces MCOLN1-induced accumulation of aberrant endosomes, indicating ALG-2 modulates MCOLN1 function in the late endosomal-lysosomal pathway. Co-immunoprecipitation, direct binding assay, deletion/point mutagenesis of MCOLN1, fluorescence microscopy with dominant-negative Vps4B The Journal of Biological Chemistry High 19864416
2010 The ALG-2-binding site (ABS) in Sec31A (aa 839-851 in Pro-rich region) controls retention kinetics of Sec31A at ERES; FRAP analysis shows ABS deletion reduces the high-affinity/slow-turnover population of Sec31A at ERES. Stable cell lines with GFP-ALG-2 and Sec31A-RFP, live-cell imaging after Ca2+ mobilization, biotin-ALG-2 overlay to map ABS, FRAP Bioscience, Biotechnology, and Biochemistry Medium 20834162
2010 Crystal structure of ALG-2(ΔGF122) in Ca2+-bound form reveals that deletion of Gly121-Phe122 shortens α-helix 5 and repositions Arg125 to partially block Pocket 1, explaining failure to bind Alix; F122A/G substitutions (but not F122W) increase Alix-binding by expanding Pocket 2, while affecting binding to TSG101 and annexin A11 differently, demonstrating structural flexibility in target recognition. X-ray crystallography, in vitro binding assays with multiple ALG-2 point mutants and Alix/TSG101/annexin A11 BMC Structural Biology High 20691033
2011 PDCD6/ALG-2 directly binds VEGFR-2 and suppresses phosphorylation of PI3K/Akt/mTOR/GSK-3β/p70S6K signaling, reducing VEGF-induced endothelial proliferation, invasion, and tube formation in vitro. Co-immunoprecipitation to show VEGFR-2 binding, Western blot of downstream signaling, cell migration/invasion/tube formation assays with recombinant PDCD6 Cellular Signalling Low 21893193
2013 ALG-2/Ca2+ attenuates COPII vesicle budding in vitro through interaction with the Pro-rich region of Sec31A; ALG-2 increases recruitment of Sec23/24 and Sec13/31A to liposomes and mediates Sec13/31A binding to Sec23; EF-hand 1 Ca2+-binding site is required for this activity. In vitro COPII budding assay with semi-intact cells and liposomes, protein recruitment assay, EF-hand 1 mutation, pulldown PLoS One High 24069399
2013 Nuclear ALG-2 interacts Ca2+-dependently with CHERP (Ca2+ homeostasis ER protein); Ca2+ mobilization recruits nuclear ALG-2 to CHERP-positive nuclear speckles; knockdown of CHERP or ALG-2 alters alternative splicing of IP3R1 pre-mRNA (inclusion of exons 41/42); CHERP binds IP3R1 RNA, indicating ALG-2 participates in nuclear pre-mRNA splicing regulation. Co-immunoprecipitation, live-cell time-lapse imaging, RNA immunoprecipitation, siRNA knockdown with RT-PCR splicing analysis The Journal of Biological Chemistry High 24078636
2013 VPS37B and VPS37C isoforms of ESCRT-I interact with ALG-2 more strongly than TSG101 does; ALG-2 functions as a Ca2+-dependent adaptor that bridges ALIX and ESCRT-I to form a ternary ESCRT-I/ALIX/ALG-2 complex, demonstrated with purified recombinant proteins. Far-Western blot with biotin-labeled ALG-2, pulldown assays, in vitro binding with purified recombinant ESCRT-I complexes and ALG-2 Bioscience, Biotechnology, and Biochemistry Medium 23924735
2014 Luminal Ca2+ depletion decreases ER-to-Golgi transport rates; disruption of ALG-2/Sec31A interactions (via Pro-rich region mutations) causes severe ER-to-Golgi transport defects in intact cells; ALG-2/Sec31A interactions are required for stability of cargo receptor p24 and proper distribution of tethering protein p115, but not for Sec31A localization to ERES per se. In intact-cell transport assays, ultrastructural analysis (EM), Ca2+ depletion, dominant-negative ALG-2 binding domain disruption, p24/p115 distribution analysis The Journal of Biological Chemistry High 25006245
2015 Crystal structure of ALG-2 complexed with Sec31A peptide (type 2 motif PXPGF) shows the peptide binds to a third hydrophobic pocket (Pocket 3); Phe85 substitution abrogates Sec31A but not Alix binding; Tyr180 substitution eliminates Alix but not Sec31A binding, demonstrating that ALG-2 uses distinct hydrophobic surfaces to recognize type 1 (PPYPXYYY) vs type 2 (PXPGF) motifs. X-ray crystallography, single amino acid substitution mutagenesis, pulldown binding assays International Journal of Molecular Sciences High 25667979
2015 Ca2+-dependent ALG-2 interaction with ALIX relieves the default intramolecular autoinhibitory interaction of ALIX, promoting CHMP4-dependent ALIX membrane association; EGFR activation increases ALG-2-ALIX interaction, and this is required for ALIX-mediated MVB sorting of activated EGFR; ALG-2 activation of ALIX does not affect cytokinetic abscission or EIAV budding. Pulldown assays, membrane fractionation, EGFR MVB sorting assay, co-transfection with dominant-negative ALIX mutants, EIAV budding assay Cell Discovery High 27462417
2016 ALG-2 promotes ER exit site (ERES) localization and Ca2+-dependent polymerization of TFG (Trk-fused gene protein); ALG-2 interacts only with the ALG-2 homodimer (not ALG-2/peflin heterodimer); TFG deletion of the ALG-2-binding motif shortens TFG half-life at ERES; ALG-2 overexpression accumulates TFG at ERES. Co-immunoprecipitation, immunostaining, live-cell time-lapse imaging (thapsigargin-induced Ca2+ rise), in vitro cross-linking polymerization assay, motif deletion analysis The FEBS Journal High 27813252
2017 ALG-2 interacts Ca2+-dependently with MISSL (MAPK1-interacting and spindle-stabilizing-like protein); MISSL and ALG-2 co-relocalize to puncta upon Ca2+ rise; knockdown of either MISSL or ALG-2 reduces secreted alkaline phosphatase secretion and delays ER-to-Golgi transport of procollagen I; MISSL and ALG-2 also interact with MAP1B, and MAP1B knockdown reverses reduced secretion caused by MISSL/ALG-2 depletion. Co-immunoprecipitation, live-cell imaging, siRNA knockdown with secretion assay (SEAP), procollagen I transport assay, epistasis by double knockdown The Journal of Biological Chemistry High 28864773
2017 ALG-2 interacts with HEBP2 (heme-binding protein 2); co-expression increases the cytoplasmic pool of ALG-2 and alters HEBP2 distribution; the ALG-2/HEBP2 complex affects mitotic spindle orientation/positioning and microtubule dynamics in cancer cells. Co-immunoprecipitation, subcellular localization imaging, mitotic spindle analysis, microtubule dynamics assay Journal of Cellular Physiology Low 28004381
2018 ALG-2 participates in plasma membrane repair; ALG-2 knockout DT-40 cells are more sensitive to electroporation; reintroduction of ALG-2 rescues this sensitivity; wild-type but not Ca2+-binding-deficient ALG-2 partially protects HeLa cells from digitonin-induced death; a peptide with the ALG-2 binding sequence of ALIX inhibits this protective function. PDCD6 gene disruption in DT-40 cells, electroporation survival assay, overexpression rescue, digitonin treatment, ALIX peptide competition PLoS One High 30240438
2018 MAP1B interacts Ca2+-dependently with ALG-2 through a region lacking canonical ABM-1/ABM-2 motifs; MAP1B binding selectively competes with ABM-2-containing proteins (e.g., Sec31A) for ALG-2; MAP1B knockout cells show increased co-localization of ALG-2 with Sec31A; overexpression of wild-type MAP1B disperses ALG-2 and Sec31A distributions. Co-immunoprecipitation, point mutagenesis of MAP1B, MAP1B knockout cells, immunofluorescence co-localization Biochemical and Biophysical Research Communications Medium 29432744
2020 ALG-2 directly interacts with Rpn3 (a component of the 26S proteasome) and regulates proteasome activity upon Ca2+ elevation following T cell activation; this modulates MCL1 stability and accelerates T cell apoptosis (contraction); ALG-2 thus couples T cell activation to the subsequent apoptotic contraction phase. Co-immunoprecipitation (ALG-2-Rpn3), proteasome activity assay, MCL1 stability assay, T cell activation and apoptosis assays Cell Death & Disease Medium 31919392
2020 PDCD6 interacts with c-Raf via Co-IP, leading to activation of the c-Raf/MEK/ERK MAPK pathway and upregulation of MYC and JUN, promoting colorectal cancer cell proliferation. Co-immunoprecipitation, mass spectrometry, RNA-seq, Western blot of MAPK pathway components, in vitro and in vivo proliferation assays Journal of Experimental & Clinical Cancer Research Low 32746883
2021 ALG-2 and peflin together constitute a hetero-bifunctional COPII regulator; at steady-state Ca2+, ALG-2/peflin heterocomplexes bound to ERES confer a buffered secretion rate, while peflin-lacking ALG-2 complexes stimulate secretion; upon Ca2+ signaling, ALG-2-dependent effects on secretion can either increase or decrease ER export depending on signaling intensity; mechanistically, depression of secretion involves decreased COPII outer shell and increased peflin at ERES, while enhancement involves increased COPII outer shell and decreased peflin. ER-to-Golgi transport assays in NRK and PC12 cells, Ca2+ mobilization by ATP, COPII protein fractionation, peflin/ALG-2 siRNA knockdowns, secretion of physiological cargoes (collagen I, SEAP) The Journal of Biological Chemistry High 34762908
2021 CDIP1 (cell death-inducing p53 target 1) interacts with ALG-2 Ca2+-dependently; ALG-2 promotes CDIP1 association with ESCRT-I (preferentially VPS37B/C-containing); co-expression of ALG-2 and ESCRT-I enhances CDIP1-induced caspase-3/7-mediated cell death; CDIP1 also binds VAPA/B via an FFAT-like motif. Co-immunoprecipitation, Ca2+-dependent pulldown, overexpression with caspase activity assay, domain deletion analysis International Journal of Molecular Sciences Medium 33503978
2022 MAT2A interacts with PDCD6 and, upon AMPK activation, facilitates methylation of PDCD6 at K90, which increases PDCD6 protein stability; K90R mutation increases apoptosis and suppresses cervical cancer cell growth under glucose deprivation. Co-immunoprecipitation, immunoblotting, mass spectrometry, AMPK pathway inhibitors, K90R point mutation, cell viability and apoptosis assays Cell Death Discovery Medium 35396512
2024 ALG-2 binds directly to acidic membranes in a Ca2+-dependent manner via electrostatic and hydrophobic interactions; charge-reversed mutants disrupt membrane recruitment; membrane binding is required for ERES localization but ESCRT-I binding can rescue membrane-binding-defective ALG-2 at lysosomes; Ca2+-dependent membrane binding and protein binding act together in cellular ALG-2 functions. Giant unilamellar vesicle (GUV) binding experiments, molecular dynamics simulations, charge-reversed mutagenesis, fluorescence imaging in cells (thapsigargin and lysosomal Ca2+ release), in vitro reconstitution with ESCRT-I Proceedings of the National Academy of Sciences USA High 38386713
2024 ALG-2, upon lysosomal Ca2+ release (e.g., GPN-induced osmotic stress or TRPML1 activation), redistributes onto lysosomes and recruits ESCRT proteins, enhancing lysosomal membrane resilience to osmotic rupture; the ALG-2(ΔGF122) splice variant defective in ESCRT binding does not confer this protection; chelating cytoplasmic Ca2+ sensitizes lysosomes to rupture. Lysosomal leakage/rupture assays (sensitive fluorescent reporters), Ca2+ chelation (BAPTA), GPN and TRPML1 agonist treatments, ALG-2 and ΔGF122 overexpression, ESCRT recruitment imaging Proceedings of the National Academy of Sciences USA High 38781205
2024 PDCD6 interacts with LDHA and downregulates lactate metabolism; PDCD6 deficiency increases LDHA activity and lactate production, leading to RUBCN lactylation at K33, which promotes RUBCN interaction with VPS34, LAP (LC3-associated phagocytosis) formation, and bactericidal activity. Co-immunoprecipitation (PDCD6-LDHA), genetic knockout in mice and macrophages, LDHA pharmacological inhibition, lactate measurement, RUBCN lactylation site identification, LAP assays, bacterial killing assays Nature Communications High 39578445
2005 PDCD6 interacts with death-associated protein kinase 1 (DAPk1); co-transfection of PDCD6 and DAPk1 additively accelerates apoptosis via a caspase-3 dependent pathway. Yeast two-hybrid screening of human ovary cDNA library, co-transfection apoptosis assay with caspase-3 readout Biotechnology Letters Low 16132846
2008 ALG-2 knockdown in HeLa cells causes G2/M cell cycle arrest and increased early apoptosis/cell death; pan-caspase inhibitor zVAD-fmk attenuates the increase in dead cells, indicating ALG-2 has an anti-apoptotic function in HeLa cells by facilitating G2/M checkpoint passage. siRNA knockdown, cell cycle analysis by flow cytometry, cell death quantification, caspase inhibitor (zVAD-fmk) rescue Biochemical and Biophysical Research Communications Medium 19013425
2020 ALG-2 interacts Ca2+-dependently with SARAF (a negative regulator of store-operated Ca2+ entry); ALG-2 overexpression interferes with NEDD4-family E3 ligase-mediated ubiquitination of SARAF at PPXY motifs proximal to the ALG-2 binding site, stabilizing SARAF; ALG-2 dimer promotes Ca2+-dependent SARAF CytD-to-CytD interactions. Semi-quantitative in vitro binding assay, pulldown with ubiquitination assay, half-life analysis, Strep-tag pulldown, Lys-to-Arg substitution mutants International Journal of Molecular Sciences Medium 32878247
2021 PDCD6 interacts with the intracellular domain of cell adhesion molecule CHL1 in a Ca2+-dependent manner (Ca2+ chelation with BAPTA-AM abolishes association); a cell-penetrating CHL1-ICD peptide inhibits both the CHL1-PDCD6 association and PDCD6/CHL1-triggered neuronal survival. Co-immunoprecipitation, GST pull-down, proximity ligation assay in mouse brain tissue and cultured neurons, BAPTA-AM Ca2+ chelation, cell-penetrating peptide inhibition FASEB BioAdvances Medium 35024572
2012 PATL1 (P-body component Pat1b) is a novel ALG-2-interacting protein; endogenous PATL1 and ALG-2 co-immunoprecipitate; a subset of ALG-2 co-localizes with PATL1 and the P-body marker DCP1A, identifying ALG-2 as having a potential role at P-bodies. In silico ABM screening, Far-Western blot, co-immunoprecipitation with endogenous proteins, immunofluorescence co-localization Journal of Biochemistry Low 22437941

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.) 451 8560270
1999 Alix, a novel mouse protein undergoing calcium-dependent interaction with the apoptosis-linked-gene 2 (ALG-2) protein. Cell death and differentiation 215 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
2003 The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting. The Journal of biological chemistry 184 12860994
2002 Alix (ALG-2-interacting protein X), a protein involved in apoptosis, binds to endophilins and induces cytoplasmic vacuolization. The Journal of biological chemistry 153 12034747
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
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
2021 Circular RNA Calm4 Regulates Hypoxia-Induced Pulmonary Arterial Smooth Muscle Cells Pyroptosis via the Circ-Calm4/miR-124-3p/PDCD6 Axis. Arteriosclerosis, thrombosis, and vascular biology 79 33657879
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 72 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
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 69 16004603
2003 Up-regulation of ALG-2 in hepatomas and lung cancer tissue. The American journal of pathology 69 12819013
2012 Developmental characterization of the microRNA-specific C. elegans Argonautes alg-1 and alg-2. PloS one 65 22448270
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 65 12445460
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
2008 Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide complex: Ca2+/EF3-driven arginine switch mechanism. Structure (London, England : 1993) 61 18940611
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
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
2004 CHMP4b is a major binding partner of the ALG-2-interacting protein Alix among the three CHMP4 isoforms. Archives of biochemistry and biophysics 55 14678797
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
2011 Programmed cell death 6 (PDCD6) inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of VEGFR-2. Cellular signalling 53 21893193
2000 Two forms of the apoptosis-linked protein ALG-2 with different Ca(2+) affinities and target recognition. The Journal of biological chemistry 51 10744743
2016 Multifaceted Roles of ALG-2 in Ca(2+)-Regulated Membrane Trafficking. International journal of molecular sciences 50 27571067
2002 ALG-2: a Ca2+ -binding modulator protein involved in cell proliferation and in cell death. Biochimica et biophysica acta 49 12445461
2005 Programmed cell death 6 (PDCD6) protein interacts with death-associated protein kinase 1 (DAPk1): additive effect on apoptosis via caspase-3 dependent pathway. Biotechnology letters 48 16132846
2010 FSH inhibits ovarian cancer cell apoptosis by up-regulating survivin and down-regulating PDCD6 and DR5. Endocrine-related cancer 47 20943720
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
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
2014 Apoptosis-linked gene-2 (ALG-2)/Sec31 interactions regulate endoplasmic reticulum (ER)-to-Golgi transport: a potential effector pathway for luminal calcium. The Journal of biological chemistry 42 25006245
2013 ALG-2 attenuates COPII budding in vitro and stabilizes the Sec23/Sec31A complex. PloS one 41 24069399
2008 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. The Journal of biological chemistry 41 18256029
2012 PDCD6 is an independent predictor of progression free survival in epithelial ovarian cancer. Journal of translational medicine 40 22369209
2006 POSH, a scaffold protein for JNK signaling, binds to ALG-2 and ALIX in Drosophila. FEBS letters 38 16698022
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 37 38781205
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
2015 ALG-2 activates the MVB sorting function of ALIX through relieving its intramolecular interaction. Cell discovery 35 27462417
2006 Nuclear translocation of the calcium-binding protein ALG-2 induced by the RNA-binding protein RBM22. Biochimica et biophysica acta 35 17045351
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 35 10486255
2016 ALG-2 interacting protein-X (Alix) is essential for clathrin-independent endocytosis and signaling. Scientific reports 34 27244115
2004 ALG-2, a multifunctional calcium binding protein? Frontiers in bioscience : a journal and virtual library 34 14977589
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
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
2003 Properties of the co-chaperone protein p23 erroneously attributed to ALG-2 (apoptosis-linked gene 2). FEBS letters 29 14675759
2018 Up-regulation of miR-20a by HPV16 E6 exerts growth-promoting effects by targeting PDCD6 in cervical carcinoma cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 29710555
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
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
2017 MicroRNA-124-3p directly targets PDCD6 to inhibit metastasis in breast cancer. Oncology letters 25 29387242
2000 The ALG-2/AIP-complex, a modulator at the interface between cell proliferation and cell death? A hypothesis. Biochimica et biophysica acta 25 11108958
2009 Alix and ALG-2 make a link between endosomes and neuronal death. Biochemical Society transactions 24 19143631
2011 PDCD6 additively cooperates with anti-cancer drugs through activation of NF-κB pathways. Cellular signalling 22 22142513
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
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 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 19 38386713
2013 ALG-2-interacting Tubby-like protein superfamily member PLSCR3 is secreted by an exosomal pathway and taken up by recipient cultured cells. Bioscience reports 19 23350699
2022 MAT2A facilitates PDCD6 methylation and promotes cell growth under glucose deprivation in cervical cancer. Cell death discovery 18 35396512
2019 ALG-2/AGO-Dependent mir-35 Family Regulates DNA Damage-Induced Apoptosis Through MPK-1/ERK MAPK Signaling Downstream of the Core Apoptotic Machinery in Caenorhabditis elegans. Genetics 18 31296532
2020 PDCD6 cooperates with C-Raf to facilitate colorectal cancer progression via Raf/MEK/ERK activation. Journal of experimental & clinical cancer research : CR 16 32746883
2012 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. Journal of biochemistry 16 22437941
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 ALG-2 and peflin regulate COPII targeting and secretion in response to calcium signaling. The Journal of biological chemistry 15 34762908
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
2024 PDCD6 regulates lactate metabolism to modulate LC3-associated phagocytosis and antibacterial defense. Nature communications 14 39578445
2018 Association of PDCD6 polymorphisms with the risk of cancer: Evidence from a meta-analysis. Oncotarget 13 29872511
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
2018 ALG-2 participates in recovery of cells after plasma membrane damage by electroporation and digitonin treatment. PloS one 11 30240438
2017 Deregulated ALG-2/HEBP2 axis alters microtubule dynamics and mitotic spindle behavior to stimulate cancer development. Journal of cellular physiology 11 28004381
2012 Genetic variation in PDCD6 and susceptibility to lung cancer. Asian Pacific journal of cancer prevention : APJCP 11 23167403
2009 The mechanism of Ca2+-dependent recognition of Alix by ALG-2: insights from X-ray crystal structures. Biochemical Society transactions 11 19143629
2023 Analysis of Dysferlin Direct Interactions with Putative Repair Proteins Links Apoptotic Signaling to Ca2+ Elevation via PDCD6 and FKBP8. International journal of molecular sciences 10 36902136
2023 PDCD6 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis through the AKT/GSK3β/β-catenin Pathway. Biomedical and environmental sciences : BES 10 37005078
2017 MiR-124 enhances cell radiosensitivity by targeting PDCD6 in nasopharyngeal carcinoma. International journal of clinical and experimental pathology 10 31966501
2015 Single nucleotide polymorphisms in PDCD6 gene are associated with the development of cervical squamous cell carcinoma. Familial cancer 10 25362542
2010 Identification and biophysical assessment of the molecular recognition mechanisms between the human haemopoietic cell kinase Src homology domain 3 and ALG-2-interacting protein X. The Biochemical journal 10 20670214
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
2022 Electroacupuncture-Regulated miR-34a-3p/PDCD6 Axis Promotes Post-Spinal Cord Injury Recovery in Both In Vitro and In Vivo Settings. Journal of immunology research 8 36132985
2021 The Argonaute Proteins ALG-1 and ALG-2 Are Linked to Stress Resistance and Proteostasis. microPublication biology 8 34723149
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 Structural recognition mechanisms between human Src homology domain 3 (SH3) and ALG-2-interacting protein X (Alix). FEBS letters 8 22641034
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
2012 Association between two single nucleotide polymorphisms of PDCD6 gene and increased endometriosis risk. Human immunology 8 23137875
2021 Interplay in neural functions of cell adhesion molecule close homolog of L1 (CHL1) and Programmed Cell Death 6 (PDCD6). FASEB bioAdvances 7 35024572
2020 miR-9875 functions in antiviral immunity by targeting PDCD6 in mud crab (Scylla paramamosain). Virulence 7 32597292
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

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