Affinage

GABARAPL1

Gamma-aminobutyric acid receptor-associated protein-like 1 · UniProt Q9H0R8

Length
117 aa
Mass
14.0 kDa
Annotated
2026-06-09
63 papers in source corpus 28 papers cited in narrative 30 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

GABARAPL1 (GEC1/Atg8L/Apg8L) is a mammalian ATG8-family ubiquitin-like protein that functions both as a membrane-conjugated autophagy effector and as a cytosolic chaperone-like trafficking scaffold (PMID:20404487, PMID:16431922). It enters the conjugation cascade after C-terminal cleavage at Gly116 by Atg4B (which alone among Atg4A/B/C processes it), forming E1 and E2 thioester intermediates with Atg7 and Atg3 respectively, becoming lipidated and associating with autophagic vesicles that co-localise with LC3 and lysosomal compartments (PMID:14530254, PMID:16704426, PMID:20404487); Atg4B and caspase-3-truncated Atg4D mediate its delipidation, the latter coupling GABARAPL1 autophagosome formation to apoptotic signalling (PMID:19549685, PMID:20404487). Once on membranes it engages selective-autophagy cargo and machinery through LIR/AIM contacts, binding NBR1, Stbd1 (glycophagy), and the upstream PI3K-complex components PIK3C3/BECN1/ATG14, with structural studies showing that variation in hydrophobic pocket 2 underlies GABARAP-subfamily binding preference over LC3 (PMID:21620860, PMID:21893048, PMID:30767700). Functionally it is required for autophagic flux, lysosome maintenance and mitochondrial quality control, and it drives selective degradation pathways including aggrephagy of ubiquitinated proteins after proteasome inhibition and autophagic turnover of signalling proteins Dvl2 and SMADs, thereby restraining Wnt/β-catenin signalling and EMT (PMID:21691068, PMID:24879149, PMID:29535191, PMID:34681055). Independently of lipidation, GABARAPL1 acts as a tubulin-binding scaffold that chaperones export-pathway trafficking of the kappa opioid receptor, GABAA receptor, GluR1 and EP3 receptor by binding the receptor C-tail and bridging vesicles to NSF for membrane fusion; this trafficking and its tumour-suppressive activity persist in the lipidation-deficient G116A mutant (PMID:15530441, PMID:16431922, PMID:19001416, PMID:21388957, PMID:28915569, PMID:33404775). Its expression is tightly transcriptionally and epigenetically controlled by Nrf1/NRF1, KDM3B, CREB-1, FoxO1, SMADs, and by DNA methylation/histone deacetylation (PMID:29535191, PMID:37326062, PMID:37658135, PMID:26474850, PMID:37380030). In vivo, GABARAPL1 is dispensable for normal hearing but essential for aminoglycoside-induced hair cell death (PMID:39928869).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 2003 High

    Established the enzyme responsible for processing GABARAPL1, defining it as a member of a shared mammalian Atg8 modification system.

    Evidence Activity-based protein profiling with electrophilic Atg8-homologue probes in cell lysates identifying Apg4B as the common processing/deconjugating protease

    PMID:14530254

    Open questions at the time
    • Did not reconstitute the full conjugation cascade
    • No demonstration of lipidated product in cells
  2. 2006 High

    Defined GABARAPL1 as the fourth mammalian Atg8 conjugation modifier by reconstituting its E1/E2 enzymatic intermediates.

    Evidence In vitro cleavage with recombinant Atg4A/B/C plus trapping of Atg7(C572S) and Atg3(C264S) intermediates and fractionation in HeLa cells

    PMID:16704426

    Open questions at the time
    • Did not identify membrane lipid acceptor in cells
    • No selective-autophagy cargo identified
  3. 2009 High

    Linked GABARAPL1 delipidation control to apoptotic signalling via caspase-cleaved Atg4D.

    Evidence In vitro caspase-3 cleavage assay, cell-based delipidation, and Atg4D siRNA with cell-death readouts

    PMID:19549685

    Open questions at the time
    • Mechanism connecting delipidation to death sensitisation not resolved
    • Did not address other GABARAPL1 functions
  4. 2010 High

    Directly demonstrated GABARAPL1 lipidation, Gly116 cleavage, and autophagic-vesicle association in cells.

    Evidence Immunofluorescence, fractionation, Atg4B delipidation assay, and co-localisation with LC3/LysoTracker under lysosomal inhibition

    PMID:20404487

    Open questions at the time
    • Did not identify specific cargo adaptors
    • Functional consequence of flux not measured
  5. 2004 Medium

    Identified GABARAPL1 as a tubulin- and GABAA-receptor-binding protein with microtubule-bundling activity, hinting at a trafficking role distinct from autophagy.

    Evidence In vitro co-sedimentation/pull-down with tubulin and GABAA receptor, tubulin polymerisation assay, and live-cell GFP imaging

    PMID:15530441

    Open questions at the time
    • Single lab
    • Physiological relevance of microtubule bundling not established in vivo
  6. 2006 High

    Established GABARAPL1 as a chaperone-like scaffold that promotes export-pathway trafficking of the kappa opioid receptor and bridges to NSF.

    Evidence Yeast two-hybrid, GST pull-down, reciprocal Co-IP, pulse-chase, and flow cytometry of surface receptor in CHO cells and rat brain extracts

    PMID:16431922

    Open questions at the time
    • Did not map exact binding residues (resolved later)
    • Generality across receptors not yet tested
  7. 2008 High

    Mapped the hydrophobic GEC1–hKOR interface at residue resolution and showed microtubule binding is required for the chaperone effect, extending the trafficking role to multiple receptors.

    Evidence Site-directed mutagenesis of both partners, pull-downs, molecular modelling, and surface-receptor imaging for GluR1 and EP3.f

    PMID:19001416

    Open questions at the time
    • No high-resolution structure of the complex
    • Single lab
  8. 2011 Medium

    Showed the trafficking-chaperone function is lipidation-independent and driven by higher GABARAPL1 affinity for receptor C-tail than GABARAP.

    Evidence G116A mutagenesis, Co-IP, GST pull-down, and surface-receptor flow cytometry

    PMID:21388957

    Open questions at the time
    • Single lab, two methods
    • Affinity quantification limited
  9. 2011 High

    Provided the first structural and thermodynamic description of a GABARAPL1–LIR (NBR1) complex, defining its selective-autophagy adaptor recognition.

    Evidence NMR structure with ITC and systematic LIR mutagenesis

    PMID:21620860

    Open questions at the time
    • Single LIR partner characterised
    • Functional consequence in cells not tested here
  10. 2011 High

    Identified GABARAPL1 as the glycophagy scaffold through a defined AIM in Stbd1.

    Evidence Reciprocal Co-IP, co-localisation, and W203A/V206A AIM mutagenesis

    PMID:21893048

    Open questions at the time
    • Did not demonstrate glycogen degradation directly
    • In vivo relevance not addressed here
  11. 2011 Medium

    Placed GABARAPL1 as a negative regulator of Wnt signalling via p62-dependent autophagic degradation of Dvl2, and a tumour suppressor.

    Evidence Yeast two-hybrid, Co-IP, 3-MA-blocked degradation, luciferase reporter, and tumour growth assays

    PMID:21691068

    Open questions at the time
    • Direct vs p62-bridged binding not separated
    • Single lab
  12. 2011 Medium

    Identified HSP90 as a stabiliser protecting GABARAPL1 from proteasomal degradation.

    Evidence GST pull-down, mass spectrometry, Co-IP, and proteasome-inhibitor rescue of 17-AAG-induced degradation

    PMID:22120110

    Open questions at the time
    • Direct vs chaperone-client geometry undefined
    • Physiological context not established
  13. 2014 Medium

    Demonstrated endogenous GABARAPL1 is required for autophagic flux, lysosome number, and mitochondrial quality control.

    Evidence shRNA knockdown with flux assays, lysosomal staining, Seahorse bioenergetics, and mitochondrial damage readouts in breast cancer cells

    PMID:24879149

    Open questions at the time
    • Single lab, one cell line
    • Mitophagy receptor not identified here
  14. 2015 Medium

    Extended the trafficking role to EGFR under hypoxia.

    Evidence siRNA knockdown with qPCR, immunoblot, flow cytometry, and surface co-localisation

    PMID:26164772

    Open questions at the time
    • Binding interface with EGFR not mapped here
    • Single lab
  15. 2015 Medium

    Defined epigenetic and CREB-1-dependent transcriptional control specific to GABARAPL1 among the family.

    Evidence Bisulfite sequencing, HDAC-inhibitor treatment, qRT-PCR, and CREB-1 ChIP in breast cancer

    PMID:26474850

    Open questions at the time
    • Upstream signals driving methylation unclear
    • Single lab
  16. 2017 Medium

    Separated GABARAPL1's tumour-suppressive function from its autophagosome-conjugation activity.

    Evidence G116A mutagenesis with flux/lysosome assays, mTOR/ULK1 immunoblotting, and xenografts

    PMID:28915569

    Open questions at the time
    • Conjugation-independent suppressive mechanism not defined
    • Single lab
  17. 2018 Medium

    Identified Nrf1 as a selective inducer of GABARAPL1 (with p62) supporting aggrephagy and survival after proteasome inhibition.

    Evidence Transcriptomics, RT-qPCR, siRNA viability assays, and Nrf1 loss-of-function with ubiquitin-conjugate imaging

    PMID:29535191

    Open questions at the time
    • Direct promoter occupancy shown later
    • Single lab
  18. 2019 High

    Provided structural basis for GABARAP-subfamily preference of upstream PI3K-complex LIRs and linked ATG14 LIR to mitophagy.

    Evidence X-ray crystallography of PIK3C3/BECN1/ATG14 LIR complexes, Co-IP, LIR mutagenesis, and mitophagy assays

    PMID:30767700

    Open questions at the time
    • GABARAPL1-specific cellular phenotypes not isolated from GABARAP
    • HP2 determinants generalisation untested
  19. 2021 Medium

    Revealed a SMAD–GABARAPL1 negative feedback loop restraining EMT through autophagic SMAD degradation.

    Evidence CRISPR/Cas9 knockout, TGF-β/TNF-α-induced EMT, Western blotting, transcriptomics, and tumour cohort IHC

    PMID:34681055

    Open questions at the time
    • Direct SMAD binding not shown
    • Two cell lines, single lab
  20. 2021 Medium

    Implicated GABARAPL1 in endosomal maturation and secretion of pro-angiogenic extracellular vesicles.

    Evidence siRNA/shRNA knockdown, electron microscopy, nanoparticle tracking, EV flow cytometry, and xenograft vascularisation

    PMID:34859607

    Open questions at the time
    • Molecular basis of endosomal role undefined
    • Single lab
  21. 2022 Medium

    Resolved the scaffold mechanism by showing GEC1 bridges KOR vesicles to NSF in a nucleotide- and domain-dependent ternary complex.

    Evidence GST pull-down with NSF domain mutants and nucleotide-bound forms, Co-IP, and competition assays

    PMID:33404775

    Open questions at the time
    • No structure of the ternary complex
    • In vivo fusion event not directly observed
  22. 2023 Medium

    Identified KDM3B as a histone-demethylase activator of GABARAPL1 transcription driving autophagy in leukemia.

    Evidence KDM3B knockout, RNA-seq, ChIP-qPCR, luciferase reporter, and autophagosome assays

    PMID:37326062

    Open questions at the time
    • Cofactors at promoter undefined
    • Single lab
  23. 2023 Medium

    Confirmed direct NRF1 promoter occupancy at GABARAPL1/p62 driving aggrephagy after proteasome dysfunction.

    Evidence Genome-wide RNA-seq, NRF1 knockdown, immunofluorescence, phospho-Ser403-p62 immunoblot, and clearance assays

    PMID:37658135

    Open questions at the time
    • Relationship to earlier Nrf1 finding not reconciled mechanistically
    • Single lab
  24. 2023 Medium

    Showed insulin represses GABARAPL1 transcription by blocking FoxO1 promoter binding to suppress hepatocyte autophagy.

    Evidence Luciferase reporter, EMSA, insulin signalling inhibitors, and autophagosome counting

    PMID:37380030

    Open questions at the time
    • Putative insulin response elements not validated in vivo
    • Single lab
  25. 2023 Medium

    Defined an LIR-independent GABARAPL1–vIRF-1 interaction required for HHV-8-driven mitophagy and viral replication, with NIX promoting the interaction.

    Evidence Co-IP, interaction-residue mutagenesis, GABARAPL1-deficient cells, and mitophagy/viral replication assays

    PMID:37459327

    Open questions at the time
    • Structural basis of LIR-independent binding unresolved
    • Single lab
  26. 2023 Medium

    Linked GABARAPL1 to EV-cargo loading and pro-metastatic potential.

    Evidence CRISPR knockout, orthotopic xenografts, EV nanoparticle tracking, mass spectrometry, and miRNA sequencing

    PMID:37898438

    Open questions at the time
    • Mechanism of cargo selection undefined
    • Single lab
  27. 2025 High

    Established a specific in vivo requirement for GABARAPL1 in aminoglycoside-induced hair cell death, dispensable for normal hearing.

    Evidence Constitutive/double GABARAP/GABARAPL1 knockout mice with auditory brainstem response, hair cell survival, and AAV-shRNA

    PMID:39928869

    Open questions at the time
    • Molecular pathway linking GABARAPL1 to ototoxicity unresolved
    • Redundancy with GABARAP partially overlapping
  28. 2026 Medium

    Connected GABARAPL1 to integrated stress response by promoting HRI activation via HSP90 for eIF2α phosphorylation and stress granule formation.

    Evidence GABARAPL1 knockout A549 cells with p-eIF2α immunoblot, stress granule imaging, and HSP90-HRI Co-IP

    PMID:41904211

    Open questions at the time
    • Whether GABARAPL1 acts directly on the HSP90-HRI complex unclear
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GABARAPL1's lipidation-independent scaffold/chaperone functions are molecularly and structurally distinguished from its membrane-conjugated autophagy roles, and how it is selected over GABARAP for specific cargo, remains unresolved.
  • No structure of a GABARAPL1 trafficking ternary complex
  • Cargo-selection determinants over GABARAP largely undefined
  • Conjugation-independent tumour-suppressive mechanism not identified

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:0008092 cytoskeletal protein binding 2 GO:0044183 protein folding chaperone 2
Localization
GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2 GO:0005768 endosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-9612973 Autophagy 5 R-HSA-9609507 Protein localization 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
ATG14ATG3ATG4BATG7HSP90NBR1NSFSTBD1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 A single protease, Apg4B/autophagin-1, acts as a processing/deconjugating enzyme for GABARAPL1 (Apg8L) and three other mammalian Atg8 homologues (GATE-16, GABARAP, MAP1-LC3), as demonstrated using electrophilic probes that form specific adducts in cell lysates. Activity-based protein profiling with electrophilic probes derived from Atg8 homologues; adduct formation in crude cell lysates The Journal of biological chemistry High 14530254
2006 Atg8L (GABARAPL1) C-terminus is cleaved by human Atg4B (but not Atg4A or Atg4C) in vitro; the processed form (Atg8L-I) forms an E1-substrate intermediate with Atg7 and an E2-substrate intermediate with Atg3, establishing it as the fourth mammalian Atg8 conjugation modifier. In vitro cleavage assay with recombinant Atg4A/B/C; co-expression with catalytic mutants Atg7(C572S) and Atg3(C264S) to trap intermediates; subcellular fractionation and fluorescence microscopy in HeLa cells The FEBS journal High 16704426
2009 Caspase-3 cleaves Atg4D in vitro and in apoptotic cells; the resulting truncated ΔN63 Atg4D shows increased activity against GABARAPL1, stimulating its delipidation. siRNA silencing of Atg4D abrogates GABARAPL1 autophagosome formation and sensitises cells to starvation- and staurosporine-induced death. In vitro caspase cleavage assay; delipidation assay in living cells; siRNA knockdown with cell death readouts; fluorescence microscopy of autophagosome markers Journal of cell science High 19549685
2010 GABARAPL1 is proteolytically cleaved at Gly116, becomes lipidated and associated with intracellular membranes, is delipidated by Atg4B, accumulates in vesicles upon lysosomal inhibition, and partially co-localises with LC3 and LysoTracker-positive structures, demonstrating its association with autophagic vesicles. Immunofluorescence microscopy; subcellular fractionation; Atg4B delipidation assay; lysosomal inhibitor treatment; co-localisation with LC3/LysoTracker Autophagy High 20404487
2004 GEC1 (GABARAPL1) interacts in vitro with tubulin and GABAA receptor, promotes tubulin assembly and microtubule bundling, and localises in perinuclear vesicles in living cells. In vitro co-sedimentation/pull-down with tubulin and GABAA receptor; GEC1-GFP live-cell imaging; tubulin polymerisation assay Biochemical and biophysical research communications Medium 15530441
2006 GEC1 (GABARAPL1) directly binds the C-tail of the human kappa opioid receptor (hKOR) via hydrophobic contacts, co-immunoprecipitates with FLAG-hKOR in CHO cells, and facilitates trafficking of hKOR from the ER/Golgi to the plasma membrane, increasing total and cell-surface KOR levels. GEC1 also interacts with N-ethylmaleimide-sensitive factor (NSF) in pull-down assays and co-immunoprecipitates with NSF in rat brain extracts. Yeast two-hybrid screening; GST pull-down; co-immunoprecipitation; pulse-chase [35S]Met/Cys labelling; flow cytometry of surface receptor; fluorescence localisation in CHO cells The Journal of biological chemistry High 16431922
2008 GEC1 interaction with hKOR requires three hKOR residues (Phe345, Pro346, Met350) and seven GEC1 residues (Tyr49, Val51, Leu55, Thr56, Val57, Phe60, Ile64), mediated by hydrophobic contacts between the kinked hKOR C-tail fragment and the curved GEC1 surface around the S2 β-strand. Microtubule binding via the GEC1 N-terminal domain is essential for the GEC1 chaperone-like effect on receptor trafficking. GEC1 also increased cell-surface levels of GluR1 and prostaglandin EP3.f receptor. Site-directed mutagenesis; pull-down assays; molecular modelling; fluorescence microscopy of surface receptor levels The Journal of biological chemistry High 19001416
2011 C-terminal modification (Gly116 cleavage and lipidation) of GEC1 is dispensable for its enhancement of hKOR expression because GEC1 binds hKOR C-tail with higher affinity than GABARAP does; the G116A mutation blocking lipidation does not impair GEC1-mediated hKOR trafficking. GABARAP, with weaker affinity, requires C-terminal modification for membrane association and KOR enhancement. Site-directed mutagenesis (G116A); co-immunoprecipitation; GST pull-down; immunofluorescence co-localisation; flow cytometry of surface receptor The Journal of biological chemistry Medium 21388957
2011 The structure of the GABARAPL1/NBR1-LIR complex was determined by NMR; the LIR motif of NBR1 (YXXV instead of canonical WXXL) binds GABARAPL1 with lower affinity than a Trp-containing LIR but substitution of other aromatic residues or addition of N-terminal negative charges does not substantially alter affinity due to enthalpy-entropy compensation. NMR structure determination; isothermal titration calorimetry (ITC); peptide binding assays with LIR mutants Journal of molecular biology High 21620860
2011 Stbd1 (starch-binding domain protein 1) interacts with GABARAPL1 via an Atg8-interacting motif (AIM: 200HEEWEMV206) located in a disordered region; single-point mutations W203A or V206A abolish co-immunoprecipitation and co-localisation, demonstrating that this AIM is necessary for Stbd1-GABARAPL1 interaction and proposing GABARAPL1 as the autophagy scaffold for glycophagy. Co-immunoprecipitation from cell extracts; immunofluorescence co-localisation; site-directed mutagenesis of AIM residues Biochemical and biophysical research communications High 21893048
2011 GABARAPL1 interacts with Dvl2 (as identified by yeast two-hybrid and co-immunoprecipitation); p62 is required for the Dvl2-GABARAPL1 interaction; GABARAPL1 mediates autophagic degradation of Dvl2 (blocked by 3-MA), thereby negatively regulating Wnt/β-catenin signalling. Yeast two-hybrid; co-immunoprecipitation; luciferase reporter assay for Wnt signalling; autophagy inhibitor (3-MA) treatment; in vitro and in vivo tumour growth assays Cellular physiology and biochemistry Medium 21691068
2011 HSP90 is a novel GABARAPL1-interacting protein, identified by GST pull-down and mass spectrometry and confirmed by co-immunoprecipitation; HSP90 inhibition (17-AAG) promotes GABARAPL1 degradation via the proteasome (blocked by MG132, bortezomib, lactacystin), indicating HSP90 protects GABARAPL1 from proteasomal degradation. GST pull-down; mass spectrometry; co-immunoprecipitation; proteasome inhibitor treatment; immunofluorescence co-localisation Biochimie Medium 22120110
2014 shRNA-mediated knockdown of endogenous GABARAPL1 in MDA-MB-436 breast cancer cells attenuates autophagic flux, decreases lysosome number, increases basal oxygen consumption and intracellular ATP, and causes accumulation of damaged mitochondria, establishing GABARAPL1 as required for autophagic flux and mitochondrial quality control. shRNA knockdown; autophagic flux assays; lysosomal staining; Seahorse bioenergetics; mitochondrial damage assessment Autophagy Medium 24879149
2017 G116A mutation in GABARAPL1 (blocking lipidation and autophagosome conjugation) impairs autophagosome/lysosome fusion and lysosome activity but does not alter mTOR or ULK1 activities, and does not affect tumour suppressive activity in vivo, demonstrating that GABARAPL1's tumour-suppressive function is independent of its autophagosome conjugation. Site-directed mutagenesis (G116A); autophagic flux assays; lysosome activity assay; mTOR/ULK1 immunoblotting; xenograft tumour growth in vivo Oncotarget Medium 28915569
2018 Proteasome inhibition selectively and rapidly induces GABARAPL1 (but not other autophagy genes) and p62 via the transcription factor Nrf1 (NFE2L1); knockdown of GABARAPL1 reduces cell survival upon proteasome inhibition; p62 knockdown blocks buildup of ubiquitinated proteins in perinuclear aggresomes. Transcriptomics/RT-qPCR; siRNA knockdown; cell viability assays; immunofluorescence of ubiquitin conjugates; Nrf1 loss-of-function The Journal of cell biology Medium 29535191
2019 PIK3C3, BECN1, and ATG14 contain functional LIR motifs that bind GABARAP and GABARAPL1 preferentially over the LC3 subfamily; crystal structures of these LIR-GABARAP/GABARAPL1 complexes revealed that variation in hydrophobic pocket 2 (HP2) explains GABARAP subfamily preference. Mutation of the ATG14 LIR blocks co-localisation with LC3B and impairs mitophagy. High-resolution X-ray crystallography; co-immunoprecipitation; site-directed mutagenesis of LIR motifs; mitophagy assays Autophagy High 30767700
2021 GABARAPL1 is required for endosomal maturation and sorting of cargo to endosomes; its silencing blocks the early endosomal pathway and impairs secretion of pro-angiogenic extracellular vesicles (EVs) during hypoxia; GABARAPL1 is expressed on the EV surface and GABARAPL1-deficient tumour xenografts show impaired vascularisation and decreased tumour growth. GABARAPL1 siRNA/shRNA knockdown; electron microscopy of endosomes; nanoparticle tracking analysis; xenograft tumour models; flow cytometry of EVs; antibody-mediated blockade of GABARAPL1+ EVs Journal of extracellular vesicles Medium 34859607
2021 During EMT induced by TGF-β/TNF-α, SMAD transcription factors drive increased GABARAPL1 expression; GABARAPL1 in turn mediates autophagic degradation of SMAD proteins, creating a negative feedback loop that restrains EMT. GABARAPL1 CRISPR/Cas9 knockout caused enhanced EMT linked to defective SMAD degradation. CRISPR/Cas9 knockout; TGF-β/TNF-α-induced EMT; Western blotting; transcriptome analysis; immunohistochemistry in lung tumour cohort Biology Medium 34681055
2022 GEC1 (GABARAPL1) interacts directly with NSF in an ADP-preferring, D1/D2 domain-dependent manner; NSF does not bind the KOR C-tail directly but forms a ternary complex via GEC1; NSF/α-SNAP do not affect KCT-GEC1 interaction. This positions GEC1 as a scaffold that bridges KOR-containing vesicles to NSF for membrane fusion along the export pathway. GST pull-down with recombinant NSF domain mutants and nucleotide-bound forms; co-immunoprecipitation; competition assays Handbook of experimental pharmacology Medium 33404775
2023 HHV-8 vIRF-1 binds directly to GABARAPL1 (preferentially over other ATG8 proteins) via an LIR-independent mechanism; specific residues in both vIRF-1 and GABARAPL1 required for mutual interaction were identified; this interaction is essential for mitophagy activation and productive HHV-8 replication. The mitophagy receptor NIX promotes vIRF-1-GABARAPL1 interaction and stabilises aggregated vIRF-1. Co-immunoprecipitation; site-directed mutagenesis; GABARAPL1-deficient cells; mitophagy assays; viral replication assays PLoS pathogens Medium 37459327
2023 The histone demethylase KDM3B activates GABARAPL1 transcription by binding to the GABARAPL1 promoter (ChIP-qPCR and luciferase assay), thereby promoting autophagosome formation and autophagic flux in leukemia cells under external stimuli. KDM3B knockout in leukemia cell lines; RNA-seq; RT-qPCR; ChIP-qPCR; luciferase reporter assay; autophagosome formation assay International journal of oncology Medium 37326062
2023 NRF1 (NFE2L1) directly targets GABARAPL1 and p62 promoters (genome-wide transcriptome analysis and functional validation); NRF1 is indispensable for p62-positive puncta formation and their co-localisation with ULK1 and TBK1, and selectively upregulates GABARAPL1 to clear ubiquitinated proteins, establishing NRF1-mediated aggrephagy after proteasome dysfunction. Genome-wide RNA-seq; NRF1 knockdown; immunofluorescence; phospho-Ser403-p62 immunoblotting; ubiquitinated protein clearance assay Scientific reports Medium 37658135
2015 GABARAPL1 is required for increased EGFR membrane expression during hypoxia; GABARAPL1 and EGFR co-localise at the plasma membrane during hypoxia, and GABARAPL1 knockdown inhibits EGFR membrane expression, placing GABARAPL1 in a trafficking role for EGFR under hypoxic conditions. qPCR; immunoblot; flow cytometry; immunocytochemistry; siRNA knockdown Radiotherapy and oncology Medium 26164772
2026 GABARAPL1 facilitates activation of the heme-regulated inhibitor kinase HRI by promoting its interaction with HSP90; in GABARAPL1-knockout A549 cells, eIF2α phosphorylation is reduced and stress granule formation is defective upon sodium arsenite treatment. GABARAPL1 knockout; immunoblotting of p-eIF2α; immunofluorescence of stress granules; co-immunoprecipitation of HSP90-HRI interaction Scientific reports Medium 41904211
2025 Targeted deletion of GABARAPL1 in mice does not affect normal hearing; however, GABARAPL1 is essential for aminoglycoside (AG)-induced hair cell death and hearing loss, as demonstrated by a GABARAPL1-knockout mouse model and confirmed in a double GABARAP/GABARAPL1 knockout. Conditional/constitutive mouse knockout; auditory brainstem response (ABR); hair cell survival assay; AAV-mediated shRNA knockdown of GABARAP in inner ear Proceedings of the National Academy of Sciences of the United States of America High 39928869
2015 DNA methylation and histone deacetylation specifically downregulate GABARAPL1 (not other GABARAP family members) in breast cancer, and CREB-1 recruitment to the GABARAPL1 promoter is required for its expression. qRT-PCR; Western blotting; bisulfite sequencing (DNA methylation); HDAC inhibitor treatment; chromatin immunoprecipitation of CREB-1 BMC cancer Medium 26474850
2024 In vitro biophysical studies (LIR-docking site interaction) show that an EGFR LIR1 peptide (FLPV) preferentially binds GABARAPL1 and GABARAP over LC3 subfamily members; X-ray crystallography demonstrates canonical binding of LIR1 core residues in both hydrophobic pockets of GABARAP, with Y49 and L50 dispensable in this context. In vitro LIR-binding assays; X-ray crystallography of GABARAP–LIR1 complex; in silico LIR prediction bioRxivpreprint Medium
2024 Deficiency of GABARAPL1 in type-2 diabetic mice is associated with diastolic dysfunction; Gabarapl1 gene delivery (AAV or similar) remediated cardiomyocyte and cardiac diastolic dysfunction in T2D mice and restored diastolic performance of human iPSC-derived 'diabetic' cardiac organoids, linking GABARAPL1-dependent glycophagy to cardiac function. Gabarapl1-knockout/deficient mice; in vivo cardiac functional measurements (echocardiography); iPSC-derived cardiac organoid model; gene delivery rescue experiment bioRxivpreprint Medium
2023 GABARAPL1 CRISPR/Cas9 deficiency in MDA-MB-231 tumours reduces pulmonary metastasis by 84% in a murine mammary fat-pad model; GABARAPL1-deficient cells migrate slower but have comparable invasive capacity; GABARAPL1 deficiency alters EV protein and miRNA content, implicating GABARAPL1 in cargo loading into pro-metastatic EVs. CRISPR/Cas9 knockout; orthotopic xenograft mouse model; nanoparticle tracking analysis; mass spectrometry of EV cargo; next-generation sequencing of EV miRNAs; scratch and transwell invasion assays Radiotherapy and oncology Medium 37898438
2023 Insulin blocks autophagy in hepatocytes by preventing FoxO1 binding to putative insulin response elements in the GABARAPL1 gene promoter, thereby repressing GABARAPL1 transcription and reducing autophagosome formation. Luciferase reporter assay; EMSA (electrophoretic mobility shift assay); insulin signalling inhibitors; autophagosome counting; Western blotting of GABARAPL1 and Beclin1 Hormone and metabolic research Medium 37380030

Source papers

Stage 0 corpus · 63 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis. Journal of cell science 219 19549685
2003 A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L. The Journal of biological chemistry 208 14530254
2011 Starch-binding domain-containing protein 1 (Stbd1) and glycogen metabolism: Identification of the Atg8 family interacting motif (AIM) in Stbd1 required for interaction with GABARAPL1. Biochemical and biophysical research communications 139 21893048
2019 Members of the autophagy class III phosphatidylinositol 3-kinase complex I interact with GABARAP and GABARAPL1 via LIR motifs. Autophagy 99 30767700
2018 Rapid induction of p62 and GABARAPL1 upon proteasome inhibition promotes survival before autophagy activation. The Journal of cell biology 92 29535191
2014 The role of GABARAPL1/GEC1 in autophagic flux and mitochondrial quality control in MDA-MB-436 breast cancer cells. Autophagy 91 24879149
2010 GABARAPL1 (GEC1) associates with autophagic vesicles. Autophagy 91 20404487
2006 GEC1 interacts with the kappa opioid receptor and enhances expression of the receptor. The Journal of biological chemistry 78 16431922
2011 Characterization of the interaction of GABARAPL-1 with the LIR motif of NBR1. Journal of molecular biology 77 21620860
2011 GABARAPL1 (GEC1): original or copycat? Autophagy 76 21597319
2015 MicroRNA-143 enhances chemosensitivity of Quercetin through autophagy inhibition via target GABARAPL1 in gastric cancer cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 68 26349981
2016 MicroRNA-195 regulates proliferation, migration, angiogenesis and autophagy of endothelial progenitor cells by targeting GABARAPL1. Bioscience reports 56 27623937
2004 GEC1, a protein related to GABARAP, interacts with tubulin and GABA(A) receptor. Biochemical and biophysical research communications 53 15530441
2003 Expression of gec1/GABARAPL1 versus GABARAP mRNAs in human: predominance of gec1/GABARAPL1 in the central nervous system. Brain research. Molecular brain research 50 14625090
2015 The autophagy GABARAPL1 gene is epigenetically regulated in breast cancer models. BMC cancer 49 26474850
2011 GABARAPL1 negatively regulates Wnt/β-catenin signaling by mediating Dvl2 degradation through the autophagy pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 48 21691068
2010 High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer. British journal of cancer 48 20197771
2006 Atg8L/Apg8L is the fourth mammalian modifier of mammalian Atg8 conjugation mediated by human Atg4B, Atg7 and Atg3. The FEBS journal 46 16704426
2021 Secretion of pro-angiogenic extracellular vesicles during hypoxia is dependent on the autophagy-related protein GABARAPL1. Journal of extracellular vesicles 31 34859607
2001 A novel early estrogen-regulated gene gec1 encodes a protein related to GABARAP. Biochemical and biophysical research communications 31 11374880
2020 Triggering a switch from basal- to luminal-like breast cancer subtype by the small-molecule diptoindonesin G via induction of GABARAPL1. Cell death & disease 30 32801338
2011 Effects of C-terminal modifications of GEC1 protein and gamma-aminobutyric acid type A (GABA(A)) receptor-associated protein (GABARAP), two microtubule-associated proteins, on kappa opioid receptor expression. The Journal of biological chemistry 29 21388957
2023 The transcription factor NRF1 (NFE2L1) activates aggrephagy by inducing p62 and GABARAPL1 after proteasome inhibition to maintain proteostasis. Scientific reports 28 37658135
2022 Loss of GABARAPL1 confers ferroptosis resistance to cancer stem-like cells in hepatocellular carcinoma. Molecular oncology 28 36062307
2014 Low expression of GABARAPL1 is associated with a poor outcome for patients with hepatocellular carcinoma. Oncology reports 28 24647565
2017 GABARAPL1 suppresses metastasis by counteracting PI3K/Akt pathway in prostate cancer. Oncotarget 26 27966458
2006 Specific distribution of gabarap, gec1/gabarap Like 1, gate16/gabarap Like 2, lc3 messenger RNAs in rat brain areas by quantitative real-time PCR. Brain research 26 16458273
2013 Specific distribution of the autophagic protein GABARAPL1/GEC1 in the developing and adult mouse brain and identification of neuronal populations expressing GABARAPL1/GEC1. PloS one 24 23690988
2017 GABARAPL1 tumor suppressive function is independent of its conjugation to autophagosomes in MCF-7 breast cancer cells. Oncotarget 23 28915569
2015 GABARAPL1 is required for increased EGFR membrane expression during hypoxia. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 23 26164772
2015 The two Dictyostelium autophagy eight proteins, ATG8a and ATG8b, associate with the autophagosome in succession. European journal of cell biology 21 26697781
2008 GEC1-kappa opioid receptor binding involves hydrophobic interactions: GEC1 has chaperone-like effect. The Journal of biological chemistry 20 19001416
2022 The hepatoprotective effects of n3-polyunsaturated fatty acids against non-alcoholic fatty liver disease in diabetic rats through the FOXO1/PPARα/GABARAPL1 signalling pathway. Life sciences 15 36336129
2019 GABARAPL1 Promotes AR+ Prostate Cancer Growth by Increasing FL-AR/AR-V Transcription Activity and Nuclear Translocation. Frontiers in oncology 14 31803623
2008 Specific regional distribution of gec1 mRNAs in adult rat central nervous system. Brain research 14 18423580
2006 Distribution and ultrastructural localization of GEC1 in the rat CNS. Neuroscience 14 16650615
2017 GABARAPL1 acts as a potential marker and promotes tumor proliferation and metastasis in triple negative breast cancer. Oncotarget 13 29088804
2020 Cytoprotective autophagy induction by withaferin A in prostate cancer cells involves GABARAPL1. Molecular carcinogenesis 12 32743846
2011 GABARAPL1 antibodies: target one protein, get one free! Autophagy 12 21862879
2023 The mitophagy receptor NIX induces vIRF-1 oligomerization and interaction with GABARAPL1 for the promotion of HHV-8 reactivation-induced mitophagy. PLoS pathogens 11 37459327
2015 Gabarapl1 mediates androgen-regulated autophagy in prostate cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 11 26050226
2022 Oxidative-Damaged Mitochondria Activate GABARAPL1-Induced NLRP3 Inflammasomes in an Autophagic-Exosome Manner after Acute Myocardial Ischemia. Oxidative medicine and cellular longevity 10 36238641
2011 Identification of HSP90 as a new GABARAPL1 (GEC1)-interacting protein. Biochimie 10 22120110
2009 Expression of the GABAA receptor associated protein Gec1 is circadian and dependent upon the cellular clock machinery in GnRH secreting GnV-3 cells. Molecular and cellular endocrinology 10 19524128
2005 Analysis of the guinea-pig estrogen-regulated gec1/GABARAPL1 gene promoter and identification of a functional ERE in the first exon. Biochimica et biophysica acta 10 16153720
2021 GABARAPL1 Inhibits EMT Signaling through SMAD-Tageted Negative Feedback. Biology 9 34681055
2023 GABARAPL1 is essential in extracellular vesicle cargo loading and metastasis development. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 5 37898438
2022 The ATG8 Family Proteins GABARAP and GABARAPL1 Target Antigen to Dendritic Cells to Prime CD4+ and CD8+ T Cells. Cells 5 36139357
2024 Poly-l-arginine promotes ferroptosis in asthmatic airway epithelial cells by modulating PBX1/GABARAPL1 axis. International journal of biological macromolecules 4 39645127
2021 The NMD Pathway Regulates GABARAPL1 mRNA during the EMT. Biomedicines 4 34680418
2025 Inhibition of GABARAP or GABARAPL1 prevents aminoglycoside- induced hearing loss. Proceedings of the National Academy of Sciences of the United States of America 3 39928869
2023 Histone lysine demethylase 3B regulates autophagy via transcriptional regulation of GABARAPL1 in acute myeloid leukemia cells. International journal of oncology 3 37326062
2022 MiR-145 inhibits the differentiation and proliferation of bone marrow stromal mesenchymal stem cells by GABARAPL1 in steroid-induced femoral head necrosis. BMC musculoskeletal disorders 3 36435763
2019 Downregulation of Gabarapl1 significantly attenuates antibody binding to porcine aortic endothelial cells. Xenotransplantation 3 31433094
2025 GABARAPL1 Exerts Regulatory Effects on Hypoxia-Induced Pyroptosis in the Pathogenesis of Myocardial Infarction. Journal of cellular and molecular medicine 2 40095893
2024 Targeting GABARAPL1/HIF-2a axis to induce tumor cell apoptosis in nasopharyngeal carcinoma. Iranian journal of basic medical sciences 2 38234672
2024 ZNF197-AS1/miR-425/GABARAPL1 axis: a novel regulatory mechanism in uveal melanoma. American journal of physiology. Cell physiology 2 39308299
2024 GABARAPL1 is essential for ACR-induced autophagic cell death of mouse Leydig cells. Ecotoxicology and environmental safety 2 39626489
2026 GABARAPL1 is important for the activation of HRI during eIF2α phosphorylation-dependent stress response to sodium arsenite. Scientific reports 0 41904211
2026 Sleeve Gastrectomy Alters Exosomal miR-497-5p Cargo to Ameliorate Metabolic Dysfunction-Associated Steatotic Liver by Targeting GABARAPL1. Diabetes, metabolic syndrome and obesity : targets and therapy 0 41982640
2026 A Conserved 3'UTR Stem-loop Directs UPF1/eIF4AIII-Dependent Regulation of GABARAPL1 mRNA. Journal of molecular biology 0 42107878
2023 Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the Promoter Region of GABARAPL1. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 0 37380030
2022 Does GEC1 Enhance Expression and Forward Trafficking of the Kappa Opioid Receptor (KOR) via Its Ability to Interact with NSF Directly? Handbook of experimental pharmacology 0 33404775

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