Affinage

MAP1LC3A

Microtubule-associated protein 1 light chain 3 alpha · UniProt Q9H492

Length
121 aa
Mass
14.3 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAP1LC3A (LC3A) is a ubiquitin-like protein that serves as a central membrane conjugate of the autophagy pathway, undergoing two-step post-translational maturation: C-terminal cleavage exposing a conserved Gly to generate cytosolic LC3-I, followed by conjugation to phosphatidylethanolamine by an ATG7 (E1)/ATG3 (E2) cascade to form membrane-bound LC3-II, with ATG4B providing the reverse delipidation activity (PMID:11060023, PMID:15325588, PMID:16300744). Lipidation on the phagophore proceeds by a defined three-step docking mechanism in which WIPI2 recruits the ATG12-ATG5-ATG16L1 E3-like complex and ATG3 positions LC3 for transfer to PE, and this lipidation can be stimulated in a cargo-dependent manner by ubiquitin-binding receptors NDP52, TAX1BP1, and OPTN (PMID:38324698, PMID:33893090). Once on autophagic membranes, LC3A recruits selective cargo by binding LIR motifs in adaptor proteins—p62/SQSTM1, NBR1, FKBP8, and the reticulophagy receptor CCPG1—through its HP2 hydrophobic pocket, which structural and fragment-screening studies establish as the primary ligandable docking site (PMID:17580304, PMID:19427866, PMID:28381481, PMID:36769070, PMID:33769048, PMID:39587067). LC3A has selective roles distinct from LC3B: it binds cardiolipin-containing membranes with higher affinity and uses N-terminal residues 14 and 18 to engage damaged mitochondria during mitophagy, and its FKBP8 partnership drives Parkin-independent mitophagy (PMID:28381481, PMID:35414338). Beyond the canonical pathway, the LC3-conjugation machinery supports non-canonical lipidation at single membranes such as damaged lysosomes via an alternative ATG12-ATG5-TECPR1 E3 complex recruited by sphingomyelin, and specifies RNA-binding-protein cargo (HNRNPK, SAFB) loading into extracellular vesicles independently of degradative autophagy (PMID:37381828, PMID:37409490, PMID:31932738). LC3A activity is further controlled by acetylation, which sequesters it as a cytosolic reserve and blocks p62 binding until nutrient depletion triggers deacetylation (PMID:30633346), and the variant-1 isoform is epigenetically silenced by promoter methylation in cancer cells, where its re-expression restores autophagosome formation and suppresses tumor growth (PMID:22249245, PMID:28808307).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 2000 High

    Established that LC3 functions through a regulated conversion from a cytosolic to a membrane-bound form, defining the molecular basis for using LC3 as an autophagosome marker.

    Evidence Immunoblotting, fractionation, and immunoelectron microscopy of processing intermediates in rat liver and cultured cells

    PMID:11060023

    Open questions at the time
    • Did not identify the enzymes mediating cleavage or membrane conjugation
    • Did not distinguish LC3A from LC3B isoform-specific behavior
  2. 2004 High

    Resolved the membrane-bound form as a lipid conjugate, defining LC3-II as LC3-PE produced by a ubiquitin-like E1/E2 cascade with a dedicated deconjugase.

    Evidence In vitro conjugation assays identifying ATG7, ATG3, and hATG4B activities

    PMID:15325588

    Open questions at the time
    • E3-like specificity factor not yet defined
    • Membrane insertion geometry unresolved
  3. 2005 Medium

    Showed LC3A and LC3B are distinct variants that both undergo the canonical processing, with Gly120 essential for cleavage and membrane targeting.

    Evidence Cloning, immunofluorescence localization, and Gly120 mutagenesis

    PMID:16300744

    Open questions at the time
    • Functional divergence between LC3A and LC3B not addressed
    • Cargo selectivity not tested
  4. 2007 High

    Defined how LC3 connects to ubiquitinated cargo by identifying the LIR-motif interaction with p62/SQSTM1, establishing the basis for selective autophagy.

    Evidence Pulldown, deletion mapping of the LC3-binding motif, and pH-sensitive degradation reporter

    PMID:17580304

    Open questions at the time
    • LC3A vs LC3B preference for p62 not separated
    • Structural docking site not yet mapped
  5. 2009 Medium

    Extended LIR-based cargo recognition by showing NBR1 binds LC3A via a distinct site and bridges polyubiquitin chains to autophagy.

    Evidence Co-IP, pulldown, and ubiquitin-chain binding assays

    PMID:19427866

    Open questions at the time
    • Single lab, no structural definition of the binding surface
    • Functional consequence in cells limited
  6. 2010 Medium

    Identified ubiquitin-independent 20S proteasomal turnover of LC3 and showed p62 binding protects LC3 from this cleavage, linking cargo engagement to LC3 stability.

    Evidence In vitro proteasome cleavage with purified components, domain mapping, and p62 inhibition

    PMID:20061800

    Open questions at the time
    • In vitro only; cellular relevance of 20S processing not established
    • Single lab
  7. 2010 Medium

    Tested PKC phosphorylation as a regulatory input and showed T6/T29 phosphorylation occurs in vitro but does not detectably control autophagy, ruling out a direct LC3 phospho-switch at these sites.

    Evidence In vitro kinase assay, nanoLC-MS/MS mapping, and phosphosite mutagenesis

    PMID:20398630

    Open questions at the time
    • Negative functional result; alternative phospho-regulation not excluded
    • Other PKC substrates in the pathway unidentified
  8. 2012 Medium

    Confirmed LC3A variant-1 is functionally competent for autophagy and revealed its epigenetic silencing as a tumor-relevant event reversible by re-expression.

    Evidence GFP-LC3Av1 localization, LC3-II immunoblot, bisulfite methylation analysis, and xenograft rescue

    PMID:22249245

    Open questions at the time
    • Mechanism linking LC3A loss to tumor growth not detailed
    • Single lab
  9. 2015 Medium

    Distinguished LC3A subcellular behavior from other family members by demonstrating nucleocytoplasmic shuttling, hinting at non-autophagosomal roles.

    Evidence Confocal microscopy and fractionation with Leptomycin B/Ivermectin transport inhibitors

    PMID:26378792

    Open questions at the time
    • Nuclear function of LC3A undefined
    • Shuttling machinery not identified
  10. 2017 High

    Established LC3A isoform selectivity in cargo recognition by showing FKBP8 binds LC3A preferentially and drives Parkin-independent mitophagy.

    Evidence Y2H, in vitro and in vivo binding, LIR mutagenesis, and mitophagy microscopy

    PMID:28381481

    Open questions at the time
    • Structural basis of LC3A selectivity over GABARAPs not resolved
    • Physiological mitophagy context limited to overexpression
  11. 2017 Medium

    Revealed a reciprocal regulatory link in which LC3 binds NEDD4 via a WXXL motif and activates its ligase activity toward SQSTM1, coupling autophagosome biogenesis to ubiquitination.

    Evidence Co-IP, WXXL mutagenesis, NEDD4 knockdown phenotyping, and EM

    PMID:28085563

    Open questions at the time
    • LC3A vs LC3B contribution not separated
    • Single lab
  12. 2019 Medium

    Defined LC3A's mitochondrial membrane recognition by showing preferential cardiolipin binding and identifying N-terminal residues 14/18 as required for clearing damaged mitochondria.

    Evidence In vitro lipid-binding, residue mutagenesis, siRNA double knockdown, and colocalization

    PMID:35414338

    Open questions at the time
    • Structural mode of cardiolipin engagement unresolved
    • Receptor coupling to residues 14/18 not defined
  13. 2019 Medium

    Identified acetylation as a switch that sequesters LC3 as a cytosolic reserve and blocks p62 binding, with deacetylation licensing autophagy upon starvation.

    Evidence FRAP diffusion measurements, Co-IP, and pulse-chase stability assays

    PMID:30633346

    Open questions at the time
    • Acetyltransferase/deacetylase enzymes not identified
    • Acetylated residues not mapped
  14. 2019 High

    Expanded LC3 function beyond degradation by showing the LC3-conjugation machinery specifies RNA-binding-protein cargo loading into extracellular vesicles (LDELS).

    Evidence BioID proteomics, EV profiling, genetic depletion of conjugation components, and RBP Co-IP

    PMID:31932738

    Open questions at the time
    • LC3A-specific contribution within the family not isolated
    • Mechanism of RBP selection at the membrane unresolved
  15. 2020 Medium

    Dissected substrate recognition by deconjugases, showing ATG4B uses a molecular-ruler mechanism on the LC3 C-terminal motif distinct from the bacterial effector RavZ.

    Evidence Semisynthetic LC3-PE cleavage assays and molecular docking

    PMID:32686895

    Open questions at the time
    • Structural snapshot of ATG4B-LC3-PE complex not provided
    • Cellular delipidation kinetics not measured
  16. 2020 Medium

    Demonstrated interdependence of ATG4B and LC3 membrane dynamics, with ATG4B activity tuning LC3 binding/dissociation kinetics to control autophagosome formation efficiency.

    Evidence Live-cell FRAP with GFP-tagged proteins and ATG4B activity mutants

    PMID:34562084

    Open questions at the time
    • Performed largely with LC3B; LC3A behavior assumed
    • Single lab
  17. 2021 High

    Reconstituted cargo-stimulated lipidation, showing NDP52, TAX1BP1, and OPTN promote LC3 lipidation with differential ULK1 dependence atop a common WIPI2/ATG core requirement.

    Evidence GUV reconstitution with purified core complexes, receptors, and model cargo

    PMID:33893090

    Open questions at the time
    • Receptor selectivity among LC3/GABARAP members not addressed
    • In vitro system lacks full membrane context
  18. 2021 Medium

    Linked LC3A loss to a concrete proteostasis defect by showing LC3A-V1 is required for aggresome vimentin cage clearance, independently of LC3B.

    Evidence siRNA silencing, adenoviral rescue, immunofluorescence, and methylation analysis

    PMID:28808307

    Open questions at the time
    • Molecular link from LC3A to vimentin cage disruption not detailed
    • Single cell model
  19. 2021 High

    Provided the structural basis for targeting LC3A by solving its complex with a small molecule, demonstrating the HP2 LIR-docking pocket is druggable.

    Evidence X-ray crystallography of LC3A-dihydronovobiocin and SAR

    PMID:33769048

    Open questions at the time
    • Cellular activity of the ligand not established
    • Selectivity over GABARAPs not shown
  20. 2022 High

    Established a PINK1-independent route to localized LC3 lipidation in which the NLRX1/RRBP1 complex couples mitochondrial protein import stress to mitophagosome formation.

    Evidence NLRX1 and PINK1 knockout comparison, RRBP1 interaction studies, lipidation assays, and in vivo muscle mitophagy

    PMID:35752171

    Open questions at the time
    • Direct LC3A vs LC3B involvement not separated
    • How RRBP1 positions the conjugation machinery unresolved
  21. 2022 High

    Defined an ATG16L1-independent E3 route for non-canonical LC3 lipidation at damaged lysosomes via an ATG12-ATG5-TECPR1 complex recruited upstream of galectin.

    Evidence TECPR1 and ATG16L1/TECPR1 double knockout epistasis, Co-IP, domain deletion, and lysosomal damage assays

    PMID:37381828 PMID:37409490

    Open questions at the time
    • Physiological breadth of the alternative pathway not fully mapped
    • Interplay with canonical ATG16L1 route during overlapping stress unclear
  22. 2023 High

    Identified the lipid signal for the alternative E3 by showing TECPR1's DysF domain binds cytosolically exposed sphingomyelin to nucleate ATG5-dependent LC3 lipidation, with a crystal structure pinpointing W154.

    Evidence Crystallography of N'DysF, W154 mutagenesis, sphingomyelin-binding assays, and ATG5 Co-IP

    PMID:37409490

    Open questions at the time
    • Structure of the assembled E3-TECPR1-membrane complex absent
    • Single lab for structural work
  23. 2023 Medium

    Connected ER stress to LC3A-mediated reticulophagy through an ATF4-MAP1LC3A-CCPG1 transcriptional and protein-interaction axis.

    Evidence ATF4 ChIP-seq on the MAP1LC3A promoter, MAP1LC3A-CCPG1 Co-IP, and RNAi in a tunicamycin ER stress model

    PMID:36769070

    Open questions at the time
    • LIR basis of the LC3A-CCPG1 interaction not mapped
    • Restricted to granulosa cell context
  24. 2023 Medium

    Identified a brake on mitophagy in which TNIP1 bridges LC3/GABARAP (including LC3A) and TAX1BP1 through bipartite LIR and AHD3 contacts to limit mitophagy rate.

    Evidence TNIP1 knockout, LIR/AHD3 domain mutagenesis, Co-IP, and mitophagy flux assays

    PMID:36898370

    Open questions at the time
    • LC3A-specific binding affinity vs other family members not quantified
    • Structural detail of the bipartite interaction lacking
  25. 2024 High

    Resolved the mechanism of LC3 lipidation as a three-step membrane docking process, assigning roles to WIPI2 recruitment, ATG16L1 helix α2, and ATG3 positioning, and nominating catalytic histidines.

    Evidence Molecular dynamics, in vitro reconstitution, mutagenesis, and in cellulo validation

    PMID:38324698

    Open questions at the time
    • Catalytic residue assignment is candidate-level
    • Dynamics specific to LC3A vs LC3B not separated
  26. 2024 High

    Generalized the druggability of the family by showing through large-scale fragment screening that HP2, not HP1, is the primary ligandable pocket within the LIR docking site of LC3A and relatives.

    Evidence Crystallographic fragment screening (~1000 structures), in silico docking, and biophysical assays

    PMID:39587067

    Open questions at the time
    • Functional inhibition of cargo binding in cells not demonstrated
    • LC3A-selective chemotypes not yet defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what distinguishes LC3A function from LC3B/LC3C at the cellular level across pathways, including the identity of the acetyltransferase/deacetylase regulating LC3A, the structural basis of its cardiolipin and isoform-selective cargo recognition, and the function of its nuclear pool.
  • No enzyme identified for LC3A acetylation cycle
  • No structure of LC3A cargo or membrane complexes with isoform-discriminating detail
  • Nuclear role of LC3A uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0031386 protein tag activity 3 GO:0098772 molecular function regulator activity 2 GO:0008289 lipid binding 1
Localization
GO:0005739 mitochondrion 3 GO:0031410 cytoplasmic vesicle 3 GO:0005764 lysosome 2 GO:0005829 cytosol 2 GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-9612973 Autophagy 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-5653656 Vesicle-mediated transport 1
Partners
ATG3ATG4BCCPG1FKBP8NBR1NEDD4SQSTM1TNIP1
Complex memberships
ATG12-ATG5-ATG16L1 E3-like complexATG12-ATG5-TECPR1 alternative E3-like complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 LC3 (MAP1LC3A/B) is post-translationally processed in two steps: first, the C-terminal 22 amino acids are removed to generate LC3-I (cytosolic form), then a fraction of LC3-I is converted to LC3-II (membrane-bound form) that specifically associates with autophagosome membranes. Mutational analyses confirmed this processing cascade, and the amount of LC3-II correlates with autophagosome number. Immunoblotting, subcellular fractionation, immunoelectron microscopy, mutational analysis in rat liver and cultured cells The EMBO journal High 11060023
2004 LC3-I is conjugated to phosphatidylethanolamine (PE) by a ubiquitin-like conjugation cascade requiring ATG7 (E1-like) and ATG3 (E2-like) enzymes to form LC3-II (LC3-PE), which inserts into autophagosomal membranes. Delipidation of LC3-II back to LC3-I is mediated by hATG4B. Biochemical conjugation assays, enzyme identification, mutational analyses The international journal of biochemistry & cell biology High 15325588
2005 LC3A and LC3B are two distinct rat variants of LC3; both undergo characteristic C-terminal cleavage and PE modification analogous to LC3, and both associate with autophagosomal membranes. The conserved Gly120 residue of LC3A and LC3B is essential for C-terminal cleavage and membrane localization. Molecular cloning, overexpression, subcellular localization by immunofluorescence, mutation analysis (Gly120) Biochemical and biophysical research communications Medium 16300744
2007 p62/SQSTM1 directly interacts with LC3A (and LC3B) through a 22-residue sequence containing an evolutionarily conserved motif (LIR motif). This interaction is required for autophagic sequestration and lysosomal degradation of p62-positive ubiquitinated protein aggregates. Direct binding assay (pulldown), deletion/mutational mapping of the LC3-binding motif, pH-sensitive fluorescent tag to track autophagic degradation The Journal of biological chemistry High 17580304
2009 NBR1 binds to LC3A via a novel binding site (distinct from the p62 LIR). This interaction, combined with NBR1's UBA domain binding to K48/K63-linked polyubiquitin chains, links NBR1 to autophagic protein turnover. Co-immunoprecipitation, pulldown, ubiquitin-chain binding assays FEBS letters Medium 19427866
2010 The 20S proteasome processes LC3 in an ATP- and ubiquitin-independent manner: it first cleaves within the ubiquitin fold of LC3, disrupting its conjugation function, and subsequently degrades LC3 completely. Processing requires both the N-terminal helices and the ubiquitin fold of LC3. p62 binding to LC3 inhibits this 20S proteasomal cleavage. Biochemical purification, in vitro proteasome cleavage assay, domain deletion mapping, inhibition by p62 Autophagy Medium 20061800
2010 Protein kinase C (PKC) directly phosphorylates LC3 at T6 and T29 in vitro, as mapped by nanoLC-MS/MS. However, mutation of these sites (singly or doubly to Ala/Asp/Glu) did not significantly affect autophagy in cells, indicating PKC regulates autophagy through a mechanism independent of LC3 phosphorylation at these residues. Orthophosphate metabolic labeling, in vitro kinase assay with purified PKC, nanoLC-MS/MS phosphopeptide mapping, site-directed mutagenesis Biochemical and biophysical research communications Medium 20398630
2012 LC3A variant-1 (LC3Av1) generates lipidated form-II and localizes to LC3B-positive autophagosomes during starvation- or p53-induced autophagy, confirming its functional role in autophagy. In cancer cell lines, LC3Av1 is frequently inactivated by aberrant promoter DNA methylation; restoration of LC3Av1 expression inhibited tumor growth in vivo. GFP-LC3Av1 localization by fluorescence microscopy, immunoblot for LC3-II, methylation analysis (bisulfite sequencing), tumor xenograft rescue experiment Oncogene Medium 22249245
2017 FKBP8 contains an N-terminal LIR motif that binds specifically and strongly to LC3A (but not efficiently to BNIP3 or NIX substrates) both in vitro and in vivo. FKBP8 recruits lipidated LC3A to damaged mitochondria in a LIR-dependent manner, and co-expression of FKBP8 with LC3A profoundly induces Parkin-independent mitophagy. Yeast two-hybrid screen, in vitro binding assays, in vivo co-immunoprecipitation, LIR mutant analysis, mitophagy assay by fluorescence microscopy EMBO reports High 28381481
2017 NEDD4 (HECT E3 ubiquitin ligase) interacts with LC3 through a conserved WXXL LIR motif and is required for autophagosomal biogenesis; LC3 functions as an activator of NEDD4 ligase activity toward SQSTM1. Co-immunoprecipitation, WXXL motif mutagenesis, NEDD4 knockdown with autophagy phenotype analysis, electron microscopy Autophagy Medium 28085563
2019 LC3A binds to cardiolipin-containing membranes with higher affinity than LC3B. Residues 14 and 18 in the N-terminal region of LC3A are important for recognition of damaged mitochondria during rotenone- or CCCP-induced mitophagy. Double silencing of LC3A and LC3B decreases CCCP-induced mitophagy. In vitro lipid-binding assays with model membranes (gradient centrifugation), site-directed mutagenesis (residues 14 and 18), siRNA knockdown, fluorescence colocalization with mitochondria Autophagy Medium 35414338
2019 Acetylation of LC3 inhibits its complex formation (detected by FRAP-based diffusion rate), blocks its interaction with the cargo receptor p62, and prevents proteasome-dependent degradation of LC3, maintaining it as a stable cytosolic reserve. Deacetylation upon nutrient depletion permits LC3–p62 interaction and autophagy. FRAP to measure LC3 diffusion/complex formation, co-immunoprecipitation to assess p62 interaction, pulse-chase for stability measurement FEBS letters Medium 30633346
2019 The LC3 conjugation machinery (LC3-lipidation system) specifies cargo loading into extracellular vesicles (EVs): RNA-binding proteins HNRNPK and SAFB interact with LC3 and are packaged into LC3-lipidated EVs. Secretion requires the LC3-conjugation machinery, nSMase2, and FAN. This 'LDELS' pathway is distinct from classical autophagy. Proximity-dependent biotinylation proteomics (BioID), proteomic and RNA profiling of EVs, genetic knockdown of LC3-conjugation components, co-immunoprecipitation of RBPs with LC3 Nature cell biology High 31932738
2020 ATG4B localizes to early autophagic membranes in an LC3B-dependent manner, and ATG4B and LC3B undergo rapid cytosol/isolation membrane exchange (measured by FRAP) but not at completed autophagosomes. ATG4B activity controls autophagosome formation efficiency by regulating LC3B membrane binding/dissociation kinetics, demonstrating interdependent roles. FRAP in live cells, GFP-tagged ATG4B and LC3B, ATG4B activity mutants Journal of molecular cell biology Medium 34562084
2021 Reconstitution experiments with giant unilamellar vesicles (GUVs) showed that cargo receptors NDP52, TAX1BP1, and OPTN stimulate LC3 lipidation on membranes in a cargo-dependent manner. All three receptors require WIPI2 and the ATG7/ATG3/ATG12-ATG5-ATG16L1 machinery; NDP52 and TAX1BP1 require ULK1, but OPTN bypasses the ULK1 requirement. In vitro reconstitution with GUVs, purified autophagy core complexes, cargo receptors, and model ubiquitinated cargo; lipidation assay Science advances High 33893090
2021 LC3A-mediated autophagy contributes to aggresome vimentin cage clearance. Silencing of MAP1LC3A-Variant1 (epigenetically inactivated by promoter methylation in a choroid plexus carcinoma line) led to failure of aggresome vimentin cage degradation; re-expression of LC3A-V1 restored formation of LC3A-positive autophagosomes and disruption of the vimentin cage, independently of MAP1LC3B. siRNA silencing of LC3A, adenoviral re-expression, immunofluorescence colocalization, methylation analysis Scientific reports Medium 28808307
2022 Mitochondrial protein import stress (MPIS) triggers localized LC3 lipidation through NLRX1 (independently of PINK1). Cytosol-retained NLRX1 recruits RRBP1, and the NLRX1/RRBP1 complex controls LC3 recruitment and lipidation at the site of mitophagosome formation. NLRX1 knockout cells, PINK1 knockout comparison, RRBP1 interaction studies, LC3 lipidation assays, in vivo skeletal muscle mitophagy Molecular cell High 35752171
2022 LC3 lipidation at damaged lysosomes occurs through an ATG16L1-independent pathway mediated by an ATG12-ATG5-TECPR1 E3-like complex. TECPR1 is recruited to damaged lysosomes via its N-terminal dysferlin domain upstream of galectin, and forms an alternative E3-like conjugation complex with ATG12-ATG5 to drive unconventional LC3 lipidation. TECPR1 knockout, ATG16L1/TECPR1 double knockout, Co-IP, domain deletion analysis, lysosomal damage assays EMBO reports High 37381828 37409490
2023 TECPR1 acts as a receptor for cytosolically exposed sphingomyelin and recruits ATG5 to form an E3 ligase complex that mediates LC3 lipidation independently of ATG16L1. The N-terminal DysF domain (N'DysF) of TECPR1 binds sphingomyelin; crystal structure of N'DysF identified W154 as essential for sphingomyelin-membrane binding and LC3 lipidation. Crystal structure determination of N'DysF domain, site-directed mutagenesis (W154), biochemical sphingomyelin-binding assays, Co-IP with ATG5 The EMBO journal High 37409490
2023 ER stress activates reticulophagy through an ATF4-MAP1LC3A-CCPG1 pathway: ATF4 transcriptionally targets MAP1LC3A (shown by ChIP-seq), and MAP1LC3A interacts directly with the reticulophagy receptor CCPG1 (shown by co-IP), mediating ER-selective autophagy in granulosa cells. ChIP-seq (ATF4 binding to MAP1LC3A promoter), co-immunoprecipitation (MAP1LC3A–CCPG1), RNAi knockdown of ATF4 and CCPG1, tunicamycin-induced ER stress model International journal of molecular sciences Medium 36769070
2023 TNIP1 negatively regulates mitophagy through bipartite interaction: an LIR motif binds LC3/GABARAP family proteins (including LC3A), and an AHD3 domain binds the autophagy receptor TAX1BP1. TNIP1 knockout accelerates mitophagy rates; the inhibitory function depends on both interaction surfaces. TNIP1 KO cells, LIR and AHD3 domain mutagenesis, co-immunoprecipitation, mitophagy flux assays Molecular cell Medium 36898370
2024 LC3 lipidation proceeds via a three-step docking mechanism on the phagophore membrane: (i) WIPI2 recruits the ATG12-ATG5-ATG16L1 E3-like complex, (ii) helix α2 of ATG16L1 contacts the membrane, and (iii) a membrane-interacting surface of ATG3 (E2) positions LC3 for transfer to PE. Molecular dynamics simulations and in vitro/in cellulo experiments identified conserved histidines near the ATG3-LC3 thioester bond as candidate catalytic residues. Molecular dynamics simulations, in vitro reconstitution, mutagenesis, in cellulo validation, WIPI2 interaction studies Science advances High 38324698
2021 Crystal structure of the LC3A–dihydronovobiocin complex (a 4-hydroxy coumarin derivative) was solved, revealing that the LIR-docking site of LC3A is ligandable by a small non-peptide molecule at the HP2 hydrophobic pocket. X-ray crystallography of LC3A–compound complex, structure-activity relationship (SAR) studies Journal of medicinal chemistry High 33769048
2024 Large-scale crystallographic fragment screening (~1000 crystal structures) of LC3/GABARAP family members, including LC3A, showed that most fragments bind to the HP2 pocket within the LIR docking site, establishing HP2 as the primary ligandable pocket. The HP1 pocket showed limited fragment engagement. Crystallographic fragment screening (~1000 structures), in silico docking, biophysical binding assays Nature communications High 39587067
2020 ATG4B and LC3-PE use distinct substrate recognition modes: Gln116, Phe119, and Gly120 of LC3-PE are required for cleavage by both ATG4B and the Legionella effector RavZ, whereas Glu117 is specific to RavZ cleavage. ATG4B uses a 'molecular ruler' mechanism absent in RavZ; Met63 and Gln64 in RavZ's active site accommodate the LC3 C-terminal motif. Semisynthetic LC3-PE proteins with C-terminal mutations, in vitro cleavage assays with ATG4B and RavZ, molecular docking Chembiochem Medium 32686895
2015 LC3A shows distinct subcellular distribution compared to LC3B and LC3C: LC3A exhibits perinuclear and nuclear localization in cancer cell lines. Blocking nuclear export with Leptomycin B causes nuclear accumulation of LC3A, while Ivermectin (blocking nuclear import) reduces accumulation, indicating LC3A shuttles between nucleus and cytoplasm. Confocal microscopy, western blot of subcellular fractions, pharmacological nuclear export/import inhibitors (Leptomycin B, Ivermectin) PloS one Medium 26378792

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. The EMBO journal 5872 11060023
2007 p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. The Journal of biological chemistry 3849 17580304
2007 How to interpret LC3 immunoblotting. Autophagy 2267 17611390
2008 LC3 and Autophagy. Methods in molecular biology (Clifton, N.J.) 1489 18425443
2004 LC3 conjugation system in mammalian autophagy. The international journal of biochemistry & cell biology 1232 15325588
2016 LC3/GABARAP family proteins: autophagy-(un)related functions. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 537 27601442
2020 The LC3-conjugation machinery specifies the loading of RNA-binding proteins into extracellular vesicles. Nature cell biology 400 31932738
2019 Allele-selective lowering of mutant HTT protein by HTT-LC3 linker compounds. Nature 390 31666698
2017 FKBP8 recruits LC3A to mediate Parkin-independent mitophagy. EMBO reports 351 28381481
2018 LC3-Associated Phagocytosis in Myeloid Cells Promotes Tumor Immune Tolerance. Cell 270 30245008
2018 The WD40 domain of ATG16L1 is required for its non-canonical role in lipidation of LC3 at single membranes. The EMBO journal 230 29317426
2017 LC3-Associated Phagocytosis and Inflammation. Journal of molecular biology 225 28847720
2019 LC3-associated phagocytosis at a glance. Journal of cell science 222 30787029
2005 Molecular cloning and characterization of rat LC3A and LC3B--two novel markers of autophagosome. Biochemical and biophysical research communications 156 16300744
2015 Autophagosome Proteins LC3A, LC3B and LC3C Have Distinct Subcellular Distribution Kinetics and Expression in Cancer Cell Lines. PloS one 150 26378792
2020 Transgenic expression of GFP-LC3 perturbs autophagy in exocrine pancreas and acute pancreatitis responses in mice. Autophagy 84 31942816
2021 ATG4 family proteins drive phagophore growth independently of the LC3/GABARAP lipidation system. Molecular cell 81 33773106
2015 Expression and clinical significances of Beclin1, LC3 and mTOR in colorectal cancer. International journal of clinical and experimental pathology 81 26097572
2010 Processing of autophagic protein LC3 by the 20S proteasome. Autophagy 81 20061800
2022 LC3 subfamily in cardiolipin-mediated mitophagy: a comparison of the LC3A, LC3B and LC3C homologs. Autophagy 80 35414338
2010 Protein kinase C inhibits autophagy and phosphorylates LC3. Biochemical and biophysical research communications 80 20398630
2019 LC3-associated phagocytosis - The highway to hell for phagocytosed microbes. Seminars in cell & developmental biology 78 31029766
2009 Interactions with LC3 and polyubiquitin chains link nbr1 to autophagic protein turnover. FEBS letters 78 19427866
2012 A transcriptional variant of the LC3A gene is involved in autophagy and frequently inactivated in human cancers. Oncogene 77 22249245
2017 The E3 ubiquitin ligase NEDD4 is an LC3-interactive protein and regulates autophagy. Autophagy 75 28085563
2011 Decreased expression of Beclin-1 and LC3 in human lung cancer. Molecular biology reports 72 21556768
2011 Beclin-1 and LC3A expression in cutaneous malignant melanomas: a biphasic survival pattern for beclin-1. Melanoma research 60 21537144
2011 "Autophagic flux" in normal mouse tissues: focus on endogenous LC3A processing. Autophagy 60 21997374
2022 Mitochondrial protein import stress regulates the LC3 lipidation step of mitophagy through NLRX1 and RRBP1. Molecular cell 58 35752171
2019 LC3-associated phagocytosis: host defense and microbial response. Current opinion in immunology 58 31247378
2019 Human LC3 and GABARAP subfamily members achieve functional specificity via specific structural modulations. Autophagy 55 30982432
2023 An ATG12-ATG5-TECPR1 E3-like complex regulates unconventional LC3 lipidation at damaged lysosomes. EMBO reports 54 37381828
2023 TECPR1 conjugates LC3 to damaged endomembranes upon detection of sphingomyelin exposure. The EMBO journal 53 37409490
2020 Novel Insights into the Cellular Localization and Regulation of the Autophagosomal Proteins LC3A, LC3B and LC3C. Cells 51 33081014
2022 Membrane dynamics of ATG4B and LC3 in autophagosome formation. Journal of molecular cell biology 50 34562084
2016 LC3-associated phagocytosis: a crucial mechanism for antifungal host defence against Aspergillus fumigatus. Cellular microbiology 48 27185357
2022 Targeting PI3Kγ/AKT Pathway Remodels LC3-Associated Phagocytosis Induced Immunosuppression After Radiofrequency Ablation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 47 35037422
2022 LC3-associated endocytosis and the functions of Rubicon and ATG16L1. Science advances 47 36288306
2021 LC3A-mediated autophagy regulates lung cancer cell plasticity. Autophagy 44 34470575
2021 Reconstitution of cargo-induced LC3 lipidation in mammalian selective autophagy. Science advances 43 33893090
2016 mRNA and protein dataset of autophagy markers (LC3 and p62) in several cell lines. Data in brief 43 27054171
2014 An activation of LC3A-mediated autophagy contributes to de novo and acquired resistance to EGFR tyrosine kinase inhibitors in lung adenocarcinoma. The Journal of pathology 43 24687913
2017 Quantification of autophagy flux using LC3 ELISA. Analytical biochemistry 42 28477964
2016 Fluorescence-based ATG8 sensors monitor localization and function of LC3/GABARAP proteins. The EMBO journal 42 28028054
2021 2AB protein of Senecavirus A antagonizes selective autophagy and type I interferon production by degrading LC3 and MARCHF8. Autophagy 39 34964697
2019 Autophagy markers LC3 and p62 accumulate in immune-mediated necrotizing myopathy. Muscle & nerve 38 31172530
2020 LC3-dependent extracellular vesicle loading and secretion (LDELS). Autophagy 37 32330402
2017 LC3-associated phagocytosis in microbial pathogenesis. International journal of medical microbiology : IJMM 37 29169848
2019 Acetylation modulates LC3 stability and cargo recognition. FEBS letters 36 30633346
2024 ZDHHC7-mediated S-palmitoylation of ATG16L1 facilitates LC3 lipidation and autophagosome formation. Autophagy 35 39087410
2023 Tethering ATG16L1 or LC3 induces targeted autophagic degradation of protein aggregates and mitochondria. Autophagy 35 37424101
2022 LC3-dependent EV loading and secretion (LDELS) promotes TFRC (transferrin receptor) secretion via extracellular vesicles. Autophagy 34 36286616
2021 Site-1 protease controls osteoclastogenesis by mediating LC3 transcription. Cell death and differentiation 33 33469231
2023 TNIP1 inhibits selective autophagy via bipartite interaction with LC3/GABARAP and TAX1BP1. Molecular cell 31 36898370
2011 LC3A-positive "stone-like" structures in cutaneous squamous cell carcinomas. The American Journal of dermatopathology 31 21430508
2024 Three-step docking by WIPI2, ATG16L1, and ATG3 delivers LC3 to the phagophore. Science advances 28 38324698
2018 Expression and significance of autophagy genes LC3, Beclin1 and MMP-2 in endometriosis. Experimental and therapeutic medicine 28 30186424
2018 LC3A, LC3B and Beclin-1 Expression in Gastric Cancer. Anticancer research 28 30504397
2014 Structural insights into E2-E3 interaction for LC3 lipidation. Autophagy 27 24413923
2022 Role for autophagy-related markers Beclin-1 and LC3 in endometriosis. BMC women's health 25 35768796
2019 FHL1 regulates myoblast differentiation and autophagy through its interaction with LC3. Journal of cellular physiology 24 31637727
2017 Safely removing cell debris with LC3-associated phagocytosis. Biology of the cell 24 28755428
2017 Methods for Studying Interactions Between Atg8/LC3/GABARAP and LIR-Containing Proteins. Methods in enzymology 23 28253953
2014 Autophagy-targeted vaccine of LC3-LpqH DNA and its protective immunity in a murine model of tuberculosis. Vaccine 23 24631071
2009 Immunohistochemical expression of MAP1LC3A and MAP1LC3B protein in breast carcinoma tissues. Journal of clinical laboratory analysis 23 19623642
2023 The Activation of Reticulophagy by ER Stress through the ATF4-MAP1LC3A-CCPG1 Pathway in Ovarian Granulosa Cells Is Linked to Apoptosis and Necroptosis. International journal of molecular sciences 22 36769070
2021 Integrated Transcriptomic and Epigenetic Study of PCOS: Impact of Map3k1 and Map1lc3a Promoter Methylation on Autophagy. Frontiers in genetics 22 33763111
2021 Demonstrating Ligandability of the LC3A and LC3B Adapter Interface. Journal of medicinal chemistry 22 33769048
2021 Inhibition of LC3-associated phagocytosis in COPD and in response to cigarette smoke. Therapeutic advances in respiratory disease 22 34852704
2018 Recruitment of LC3 to damaged Golgi apparatus. Cell death and differentiation 22 30349077
2023 LC3-associated phagocytosis promotes glial degradation of axon debris after injury in Drosophila models. Nature communications 21 37248218
2023 Deacetylation of ATG7 drives the induction of macroautophagy and LC3-associated microautophagy. Autophagy 21 37999993
2017 Semisynthesis of autophagy protein LC3 conjugates. Bioorganic & medicinal chemistry 21 28583805
2017 LC3A Silencing Hinders Aggresome Vimentin Cage Clearance in Primary Choroid Plexus Carcinoma. Scientific reports 21 28808307
2024 LC3-associated phagocytosis of neutrophils triggers tumor ferroptotic cell death in glioblastoma. The EMBO journal 20 38806658
2020 Distinct Mechanisms for Processing Autophagy Protein LC3-PE by RavZ and ATG4B. Chembiochem : a European journal of chemical biology 20 32686895
2018 SFTS phlebovirus promotes LC3-II accumulation and nonstructural protein of SFTS phlebovirus co-localizes with autophagy proteins. Scientific reports 20 29588492
2018 Microtubule-Associated Protein 1 Light Chain 3 (LC3) Isoforms in RPE and Retina. Advances in experimental medicine and biology 20 29721994
2022 LAPped in Proof: LC3-Associated Phagocytosis and the Arms Race Against Bacterial Pathogens. Frontiers in cellular and infection microbiology 19 35047422
2017 Inhibition of autophagy protein LC3A as a therapeutic target in ovarian clear cell carcinomas. Journal of gynecologic oncology 19 28382796
2017 Sodium cantharidinate induces HepG2 cell apoptosis through LC3 autophagy pathway. Oncology reports 19 28677738
2013 The "stone-like" pattern of LC3A expression and its clinicopathologic significance in hepatocellular carcinoma. Biochemical and biophysical research communications 19 23333394
2023 CAB39 promotes cisplatin resistance in bladder cancer via the LKB1-AMPK-LC3 pathway. Free radical biology & medicine 18 37726090
2021 Beclin-1/LC3-II dependent macroautophagy was uninfluenced in ischemia-challenged vascular endothelial cells. Genes & diseases 18 35224166
2020 The LC3-conjugation machinery specifies cargo loading and secretion of extracellular vesicles. Autophagy 18 32401566
2019 Niclosamide Triggers Non-Canonical LC3 Lipidation. Cells 18 30875964
2024 Enhancement of LC3-associated efferocytosis for the alleviation of intestinal inflammation. Autophagy 17 38311819
2023 Does decreased autophagy and dysregulation of LC3A in astrocytes play a role in major depressive disorder? Translational psychiatry 17 38001115
2020 Aichi virus 3C protease modulates LC3- and SQSTM1/p62-involved antiviral response. Theranostics 17 32802187
2015 Expression of LC3, LAMP2, KEAP1 and NRF2 in Salivary Adenoid Cystic Carcinoma. Pathology oncology research : POR 17 26350055
2024 Critical assessment of LC3/GABARAP ligands used for degrader development and ligandability of LC3/GABARAP binding pockets. Nature communications 16 39587067
2022 A Multifaceted Hit-Finding Approach Reveals Novel LC3 Family Ligands. Biochemistry 16 34985287
2022 Ceramide enhances binding of LC3/GABARAP autophagy proteins to cardiolipin-containing membranes. International journal of biological macromolecules 16 35839958
2020 Detection of LC3-Associated Phagocytosis (LAP). Current protocols in cell biology 16 32436654
2018 Blocking LC3 lipidation and ATG12 conjugation reactions by ATG7 mutant protein containing C572S. Biochemical and biophysical research communications 16 30503495
2024 Promising and challenging phytochemicals targeting LC3 mediated autophagy signaling in cancer therapy. Immunity, inflammation and disease 15 39436197
2022 Cereulide and Deoxynivalenol Increase LC3 Protein Levels in HepG2 Liver Cells. Toxins 15 35202179
2022 An optimized protocol for immuno-electron microscopy of endogenous LC3. Autophagy 15 35387562
2021 Overexpression of ATG8/LC3 enhances wound-induced somatic reprogramming in Physcomitrium patens. Autophagy 15 34612155
2016 Size, organization, and dynamics of soluble SQSTM1 and LC3-SQSTM1 complexes in living cells. Autophagy 15 27442348

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