Affinage

GABARAPL1

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

Length
117 aa
Mass
14.0 kDa
Annotated
2026-04-28
62 papers in source corpus 28 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GABARAPL1 is an ATG8-family ubiquitin-like protein that functions at the intersection of selective autophagy, receptor trafficking, and cellular stress responses. After C-terminal processing at Gly116 by Atg4B and conjugation to phosphatidylethanolamine via the Atg7/Atg3 cascade, GABARAPL1 associates with autophagosomal membranes where it engages selective autophagy receptors—including Stbd1 (glycophagy), NBR1, and p62/Dvl2—through LIR/AIM motifs, and promotes autophagosome–lysosome fusion required for mitochondrial quality control, aggrephagy, and SMAD protein turnover (PMID:14530254, PMID:16704426, PMID:20404487, PMID:21893048, PMID:21620860, PMID:24879149, PMID:37658135). Independent of lipidation, GABARAPL1 promotes intracellular trafficking of cargo receptors (κ-opioid receptor, GABAA receptor, EGFR) from the ER/Golgi to the plasma membrane through direct interactions with tubulin and NSF, facilitates endosomal maturation and extracellular vesicle secretion, and scaffolds the HSP90–HRI kinase complex during integrated stress responses (PMID:16431922, PMID:19001416, PMID:21388957, PMID:34859607, PMID:41904211). Transcription of GABARAPL1 is directly activated by ERα, NRF1 upon proteasome stress, SMAD factors during EMT, KDM3B, and the circadian factor Per1, placing it under multi-signal transcriptional control (PMID:16153720, PMID:29535191, PMID:34681055, PMID:37326062, PMID:19524128).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2001 Medium

    Identification of GABARAPL1 as an estrogen-induced GABARAP-family member with a tubulin-binding motif established it as a candidate microtubule-associated protein with potential roles in membrane trafficking.

    Evidence cDNA cloning and sequence analysis from estrogen-treated cells

    PMID:11374880

    Open questions at the time
    • No functional data beyond sequence homology
    • Estrogen regulation mechanism not yet defined
  2. 2003 High

    Demonstrating that Atg4B is the specific protease that both primes and deconjugates GABARAPL1 placed it within the ATG8 conjugation machinery and implied it undergoes lipid modification like other Atg8 homologues.

    Evidence Activity-based probes and in vitro protease assays across mammalian Atg4 family members

    PMID:14530254

    Open questions at the time
    • Downstream conjugation to PE not yet shown for GABARAPL1 specifically
    • In vivo processing kinetics unknown
  3. 2004 Medium

    Showing that GABARAPL1 directly binds tubulin and GABAA receptors and promotes microtubule bundling established a non-autophagy function in receptor trafficking along microtubules.

    Evidence In vitro tubulin binding/polymerization assay and GFP-fusion live-cell imaging

    PMID:15530441

    Open questions at the time
    • Functional consequence for GABAA receptor surface expression not tested
    • Binding affinities not quantified
  4. 2005 Medium

    Mapping an ERα-responsive ERE in exon 1 provided the molecular mechanism for estrogen-dependent GABARAPL1 transcription, explaining the original discovery context.

    Evidence Luciferase reporter assay and EMSA in estrogen-treated cells

    PMID:16153720

    Open questions at the time
    • Physiological relevance of estrogen regulation in specific tissues not demonstrated
    • Other transcription factor inputs not yet explored
  5. 2006 High

    Reconstitution of the full Atg7→Atg3 conjugation cascade for GABARAPL1 and demonstration of its membrane-associated lipidated form colocalizing with LC3 established GABARAPL1 as a bona fide autophagosome-associated ATG8-family protein.

    Evidence E1/E2 intermediate trapping with active-site mutants, subcellular fractionation, and confocal microscopy in HeLa cells

    PMID:16704426

    Open questions at the time
    • Functional distinction from LC3 and GABARAP in autophagy not yet defined
    • PE conjugation not directly confirmed by mass spectrometry
  6. 2006 High

    Discovery that GABARAPL1 directly binds the κ-opioid receptor C-tail and NSF, localizes to ER/Golgi, and facilitates KOR ER-to-plasma membrane trafficking established a lipidation-independent cargo trafficking function distinct from autophagy.

    Evidence Yeast two-hybrid, GST pull-down, co-IP, pulse-chase metabolic labeling, and immunofluorescence in CHO cells and rat brain

    PMID:16431922

    Open questions at the time
    • Mechanism of NSF cooperation in vesicle fusion not resolved
    • Whether trafficking function generalizes beyond KOR unclear
  7. 2008 High

    Systematic mutagenesis of both GABARAPL1 and KOR mapped the hydrophobic interaction interface and revealed that generalized FPXXM/FPXM motifs enable GABARAPL1-mediated surface expression of multiple receptors (GluR1, EP3.f), broadening the trafficking function beyond a single receptor.

    Evidence Mutagenesis of seven GABARAPL1 residues and three KOR residues with pull-down and surface expression readouts

    PMID:19001416

    Open questions at the time
    • Structural basis of selectivity among ATG8 paralogues for receptor cargo not resolved
    • In vivo validation of multi-receptor trafficking lacking
  8. 2009 High

    Identification of caspase-3-activated Atg4D as a specific delipidase for GABARAPL1 linked apoptotic signaling to GABARAPL1 autophagosome dynamics, adding regulatory complexity beyond Atg4B.

    Evidence In vitro caspase cleavage, delipidation assay, and siRNA-mediated loss of GABARAPL1 puncta formation

    PMID:19549685

    Open questions at the time
    • Physiological contexts where Atg4D preferentially regulates GABARAPL1 over other ATG8s not established
    • Whether this links autophagy to apoptosis execution in vivo unresolved
  9. 2010 High

    Confirmation that endogenous GABARAPL1 is cleaved at Gly116, lipidated, and accumulates on autophagic vesicles upon lysosomal inhibition validated it as a functional autophagosome marker at endogenous levels.

    Evidence Immunoblot lipidation shift, bafilomycin treatment, and colocalization with LC3 and LysoTracker

    PMID:20404487

    Open questions at the time
    • Unique cargo specificity versus LC3 subfamily not delineated
  10. 2011 High

    Structural and biochemical characterization of GABARAPL1 interactions with selective autophagy receptors—NBR1 (NMR structure), Stbd1 (AIM-dependent glycophagy), Dvl2/p62 (Wnt suppression), and HSP90 (stability)—defined GABARAPL1 as a versatile LIR-binding scaffold in multiple selective autophagy pathways.

    Evidence NMR structure of NBR1-LIR/GABARAPL1 complex with ITC; Stbd1 AIM mutagenesis with co-IP; Dvl2/p62 Y2H and co-IP with autophagy inhibitor; HSP90 identification by MS and proteasome inhibitor rescue

    PMID:21620860 PMID:21691068 PMID:21893048 PMID:22120110

    Open questions at the time
    • Relative preference of GABARAPL1 vs. other ATG8s for each receptor not systematically compared
    • Glycophagy function not validated in vivo
    • HSP90 interaction interface not mapped
  11. 2011 Medium

    Demonstration that GABARAPL1's G116A mutant (lipidation-deficient) still enhances KOR surface expression showed that the receptor trafficking function is mechanistically separable from autophagosome membrane association.

    Evidence G116A mutagenesis with co-IP and surface expression readout

    PMID:21388957

    Open questions at the time
    • Whether unlipidated GABARAPL1 uses the same or different interactome for trafficking versus autophagy unknown
  12. 2014 Medium

    Knockdown of GABARAPL1 in breast cancer cells caused accumulation of damaged mitochondria and increased basal respiration, establishing a requirement for GABARAPL1 in mitochondrial quality control via autophagy.

    Evidence shRNA knockdown with autophagic flux, Seahorse bioenergetic, and mitochondrial morphology assays

    PMID:24879149

    Open questions at the time
    • Whether effect is through mitophagy specifically or general autophagy impairment not distinguished
    • Mitophagy receptors mediating GABARAPL1 recruitment not identified
  13. 2017 Medium

    Separating lipidation-dependent (autophagosome–lysosome fusion) from lipidation-independent (tumor suppression) GABARAPL1 functions through G116A mutant analysis clarified that GABARAPL1 contributes to distinct cellular processes through different biochemical modes.

    Evidence G116A mutagenesis with autophagosome–lysosome fusion assay, lysosome activity assay, and xenograft tumor growth

    PMID:28915569

    Open questions at the time
    • Molecular mechanism of lipidation-independent tumor suppression not identified
    • Whether fusion defect is direct or indirect not resolved
  14. 2018 High

    Discovery that proteasome inhibition selectively induces GABARAPL1 via NRF1, and that GABARAPL1 knockdown reduces survival during proteasome stress, revealed GABARAPL1 as a specific pro-survival effector in proteotoxic stress rather than a generic autophagy component.

    Evidence Quantitative proteomics, NRF1 knockdown, GABARAPL1 siRNA, and cell viability upon proteasome inhibition

    PMID:29535191

    Open questions at the time
    • Whether NRF1 induction of GABARAPL1 operates through aggrephagy or another degradation pathway not defined
  15. 2019 High

    Crystal structures of LIR-containing PI3K complex I subunits (PIK3C3, BECN1, ATG14) bound to GABARAPL1 and GABARAP explained the GABARAP-subfamily selectivity through HP2 pocket variation, providing the structural basis for preferential recruitment of these complexes.

    Evidence X-ray crystallography, ITC, co-IP, LIR mutagenesis, and mitophagy assay

    PMID:30767700

    Open questions at the time
    • Whether GABARAPL1 and GABARAP are redundant or have distinct roles in PtdIns3K-C1 recruitment not resolved
  16. 2021 High

    GABARAPL1 was shown to be required for endosomal maturation, cargo sorting, and secretion of pro-angiogenic extracellular vesicles during hypoxia, extending its membrane-trafficking functions beyond autophagy and ER/Golgi export to the endosomal–EV pathway.

    Evidence siRNA/shRNA knockdown with electron microscopy, nanoparticle tracking, EV surface analysis, and tumor xenograft

    PMID:34859607

    Open questions at the time
    • Molecular mechanism of GABARAPL1 action in endosomal maturation not defined
    • Whether lipidation is required for EV biogenesis function unknown
  17. 2021 Medium

    Identification of a SMAD→GABARAPL1→autophagic SMAD degradation negative feedback loop during EMT established GABARAPL1 as a node linking TGF-β signaling to autophagy-dependent signal attenuation.

    Evidence CRISPR knockout, TGF-β/TNF-α treatment, immunoblot for SMAD proteins, and transcriptome analysis

    PMID:34681055

    Open questions at the time
    • Which SMAD isoforms are direct degradation substrates not specified
    • Whether this feedback operates in non-cancer epithelial cells unknown
  18. 2023 High

    ChIP-qPCR confirmation that NRF1 directly binds the GABARAPL1 promoter and that NRF1-induced GABARAPL1 is required for aggrephagy (clearance of ubiquitinated aggregates with p62 and TBK1) consolidated the proteasome-stress–aggrephagy axis.

    Evidence ChIP-qPCR, luciferase reporter, NRF1 knockdown, immunofluorescence for p62/ULK1/TBK1 puncta

    PMID:37658135

    Open questions at the time
    • Whether GABARAPL1 directly recruits p62-positive condensates or acts upstream via PI3K complex not resolved
  19. 2023 High

    The HHV-8 viral protein vIRF-1 was found to preferentially bind GABARAPL1 over other ATG8 members via an LIR-independent mechanism, co-opting GABARAPL1 for virus-induced mitophagy required for productive viral replication—demonstrating pathogen exploitation of GABARAPL1 specificity.

    Evidence Reciprocal co-IP, mutagenesis of both partners, GABARAPL1 knockout, mitophagy and viral replication assays

    PMID:37459327

    Open questions at the time
    • Structural basis of LIR-independent vIRF-1 binding not determined
    • Whether other viruses exploit GABARAPL1 specificity unknown
  20. 2025 High

    Targeted deletion of GABARAPL1 in mice prevented aminoglycoside-induced hair cell death without affecting normal hearing, revealing an in vivo requirement for GABARAPL1 in ototoxic cell death that is partially redundant with GABARAP.

    Evidence GABARAPL1 single and GABARAP/GABARAPL1 double knockout mice with auditory brainstem response and hair cell survival quantification

    PMID:39928869

    Open questions at the time
    • Whether protection is through blocked autophagy/mitophagy in hair cells or another mechanism not resolved
    • Degree of functional redundancy with GABARAPL2 not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) what confers cargo selectivity of GABARAPL1 versus other ATG8 paralogues in different selective autophagy and trafficking pathways; (2) the structural basis and full interactome of lipidation-independent functions; (3) in vivo validation of glycophagy and SMAD-feedback roles; and (4) whether GABARAPL1's endosomal/EV functions require lipidation.
  • No systematic paralogue-separation study across all ATG8 family members
  • No in vivo glycophagy phenotype reported
  • Lipidation requirement for EV biogenesis not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0031386 protein tag activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005576 extracellular region 1 GO:0005768 endosome 1 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-9612973 Autophagy 9 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-9609507 Protein localization 3 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2
Partners
ATG3ATG4BATG7HSP90AA1NBR1NSFSQSTM1STBD1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 GABARAPL1 (GEC1) was identified as an early estrogen-regulated gene encoding a protein with an N-terminal tubulin-binding motif, closely related to GABARAP, establishing it as a new microtubule-associated protein family member. cDNA cloning, sequence analysis, 5'-RACE Biochemical and biophysical research communications Medium 11374880
2003 A single protease, Apg4B (autophagin-1), processes GABARAPL1 (Apg8L) C-termini for conjugation, acting as both a priming and deconjugating enzyme for GABARAPL1 and other mammalian Atg8 homologues. Electrophilic activity-based probes, in vitro protease activity assay, affinity labeling in cell lysates The Journal of biological chemistry High 14530254
2004 GABARAPL1 (GEC1) interacts directly with tubulin in vitro and with the GABAA receptor, and promotes tubulin polymerization and microtubule bundling; GEC1-GFP localizes to perinuclear vesicles in cytoplasm. In vitro binding assay, tubulin polymerization assay, GFP fusion live-cell imaging Biochemical and biophysical research communications Medium 15530441
2005 An estrogen response element (ERE) located in the first exon of GABARAPL1 is sufficient for estradiol-induced transcription via ERα, establishing the molecular mechanism of estrogen regulation. Transfection reporter assay, gel shift (EMSA) Biochimica et biophysica acta Medium 16153720
2006 GABARAPL1 (GEC1) interacts directly with the C-tail of the kappa opioid receptor (hKOR) via a hydrophobic interaction, co-immunoprecipitates with FLAG-hKOR in CHO cells, and facilitates trafficking of hKOR from ER/Golgi to plasma membrane, increasing total and cell-surface receptor levels. GEC1 also interacts with NSF (N-ethylmaleimide-sensitive factor) in pull-down assays and co-immunoprecipitates with NSF from rat brain. GEC1 localizes to Golgi apparatus and ER. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, pulse-chase metabolic labeling, immunofluorescence The Journal of biological chemistry High 16431922
2006 GABARAPL1 (Atg8L/Apg8L) undergoes C-terminal processing by human Atg4B (but not Atg4A or Atg4C), forms E1-substrate intermediate with Atg7 and E2-substrate intermediate with Atg3, and its modified (lipidated) form accumulates in the pelletable fraction; CFP-Atg8L colocalizes with YFP-LC3 in HeLa cells in the presence of lysosomal protease inhibitors. In vitro cleavage assay, E1/E2 intermediate trapping with active-site mutants, subcellular fractionation, confocal microscopy The FEBS journal High 16704426
2008 Three hKOR residues (Phe345, Pro346, Met350) and seven GEC1 residues (Tyr49, Val51, Leu55, Thr56, Val57, Phe60, Ile64) are indispensable for the GEC1-hKOR interaction; the interaction is hydrophobic; microtubule binding via the GEC1 N-terminal domain is essential for GEC1's effect on KOR expression. GEC1 also enhances cell surface levels of GluR1 and EP3.f receptor via similar FPXXM/FPXM motifs. Mutagenesis, pull-down assay, immunofluorescence, molecular modeling The Journal of biological chemistry High 19001416
2009 Caspase-3 cleaves Atg4D in vitro and in apoptotic cells; truncated ΔN63 Atg4D displays increased processing/delipidation activity specifically against GABARAPL1 in vitro and in living cells; siRNA silencing of Atg4D abrogates GABARAPL1 autophagosome formation. In vitro caspase cleavage assay, in vitro delipidation assay, siRNA knockdown, cell-based autophagosome assay Journal of cell science High 19549685
2009 GEC1 expression is circadian and depends on the Per1 clock gene in GnRH-secreting neurons; GEC1 is co-expressed with GABAA receptor in hypothalamic GnRH neurons; GABAA receptor levels at the cell membrane are temporally modulated, suggesting GEC1 drives circadian GABAA receptor trafficking. qPCR oscillation analysis, siRNA knockdown of Per1, serum-shock circadian synchronization, immunofluorescence Molecular and cellular endocrinology Medium 19524128
2010 GABARAPL1 is cleaved at conserved Gly116, becomes lipid-conjugated, associates with intracellular membranes, accumulates in vesicles upon lysosomal inhibition, and partially colocalizes with LC3 and LysoTracker in autophagic vesicles, demonstrating its role as an autophagosome-associated protein. Immunoblot (lipidation shift), lysosomal inhibitor treatment, immunofluorescence colocalization, subcellular fractionation Autophagy High 20404487
2011 An Atg8-interacting motif (AIM: HEEWEMV, residues 200-206) in Stbd1 is required for direct interaction with GABARAPL1; single point mutations W203A or V206A abolish co-immunoprecipitation and co-localization, suggesting GABARAPL1 acts as the autophagy machinery receptor for Stbd1-mediated glycophagy (glycogen delivery to lysosomes). Co-immunoprecipitation, immunofluorescence colocalization, site-directed mutagenesis Biochemical and biophysical research communications High 21893048
2011 NMR structure of the GABARAPL1/NBR1-LIR complex was determined; a tryptophan residue in the LIR motif increases binding affinity; substitution by other aromatic amino acids or addition of N-terminal negative charges has little net effect on affinity due to enthalpy-entropy compensation. NMR structure determination, isothermal titration calorimetry (ITC), mutagenesis Journal of molecular biology High 21620860
2011 GABARAPL1 interacts with Dvl2 (as shown by yeast two-hybrid and co-immunoprecipitation); p62 is required for the Dvl2-GABARAPL1 interaction; GABARAPL1 mediates autophagic degradation of Dvl2, thereby repressing Wnt/β-catenin signaling; 3-methyladenine (autophagy inhibitor) blocks Dvl2 degradation by GABARAPL1. Yeast two-hybrid, co-immunoprecipitation, luciferase reporter assay, 3-MA inhibition, knockdown/overexpression Cellular physiology and biochemistry Medium 21691068
2011 HSP90 was identified as a novel GABARAPL1-interacting protein by GST pull-down, mass spectrometry, and co-immunoprecipitation; HSP90 inhibition with 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, HSP90 inhibitor treatment, proteasome inhibitor rescue Biochimie Medium 22120110
2011 C-terminal modification of GABARAPL1 (GEC1) at conserved Gly116 is not required for its ability to enhance kappa opioid receptor (hKOR) expression, because GEC1 binds hKOR more strongly than GABARAP and can be recruited sufficiently without membrane association; GABARAP requires C-terminal lipidation for KOR enhancement due to weaker KOR affinity. Site-directed mutagenesis (G116A), co-immunoprecipitation, immunofluorescence, GST pull-down The Journal of biological chemistry Medium 21388957
2014 Knockdown of endogenous GABARAPL1 in breast cancer cells attenuates autophagic flux, decreases lysosome number, increases basal oxygen consumption and ATP, and causes accumulation of damaged mitochondria, demonstrating GABARAPL1 is required for mitochondrial quality control via autophagy. shRNA knockdown, autophagic flux assay (bafilomycin treatment), Seahorse bioenergetics, mitochondria morphology analysis Autophagy Medium 24879149
2017 GABARAPL1 conjugation to autophagosomes (lipidation) is required for autophagosome/lysosome fusion and lysosome activity, but not for tumor growth suppression in vivo; the G116A mutation (which prevents lipidation) reveals GABARAPL1 plays distinct roles in early versus late stages of autophagy independent of lipidation. G116A mutagenesis, autophagosome/lysosome fusion assay, lysosome activity assay, in vivo tumor xenograft Oncotarget Medium 28915569
2018 Proteasome inhibition selectively and dramatically induces GABARAPL1 (but not other autophagy genes) via the transcription factor Nrf1 (NFE2L1); GABARAPL1 knockdown reduces cell survival upon proteasome inhibition, indicating a pro-survival role distinct from bulk autophagy. Quantitative proteomics/RNA analysis, Nrf1 knockdown, GABARAPL1 siRNA knockdown, cell viability assay The Journal of cell biology High 29535191
2019 PIK3C3/VPS34, BECN1, and ATG14, core components of the autophagy PI3K complex I (PtdIns3K-C1), contain functional LIR motifs that interact with GABARAP and GABARAPL1 with preference for the GABARAP subfamily; crystal structures of these LIR-GABARAP/GABARAPL1 complexes were solved; variation in hydrophobic pocket 2 (HP2) explains GABARAP subfamily selectivity; LIR mutation in ATG14 impairs mitophagy. Crystal structure determination, isothermal titration calorimetry, co-immunoprecipitation, LIR mutagenesis, mitophagy assay Autophagy High 30767700
2019 GABARAPL1 is required for increased EGFR plasma membrane expression during hypoxia; GABARAPL1 and EGFR co-localize at the plasma membrane under hypoxia; GABARAPL1 knockdown inhibits hypoxia-induced EGFR membrane expression. Flow cytometry, immunofluorescence colocalization, siRNA knockdown, immunoblot Radiotherapy and oncology Medium 26164772
2021 GABARAPL1 is required for endosomal maturation, cargo sorting to endosomes, and secretion of pro-angiogenic extracellular vesicles (EVs) during hypoxia; GABARAPL1 silencing blocks the early endosomal pathway and impairs EV secretion; GABARAPL1 is present on the EV surface. siRNA/shRNA knockdown, electron microscopy, nanoparticle tracking, flow cytometry of EVs, angiogenesis assay, tumor xenograft Journal of extracellular vesicles High 34859607
2021 EMT induction via TGF-β/TNF-α increases GABARAPL1 expression through SMAD family transcription factors; GABARAPL1 knockout (CRISPR/Cas9) induces EMT linked to impaired autophagic degradation of SMAD proteins, establishing a SMAD→GABARAPL1→autophagy-mediated SMAD degradation negative feedback loop. CRISPR/Cas9 knockout, TGF-β/TNF-α treatment, immunoblot for SMAD proteins, transcriptome analysis, IHC Biology Medium 34681055
2022 GEC1 (GABARAPL1) interacts with NSF directly, preferring ADP-bound NSF over ATP-bound NSF; D1 and/or D2 domains of NSF interact with GEC1; NSF does not bind KOR C-tail directly but forms a complex via GEC1; this GEC1-NSF interaction may facilitate vesicle fusion along the KOR export pathway. GST pull-down with NSF domain mutants, pull-down with nucleotide-bound NSF forms Handbook of experimental pharmacology Medium 33404775
2023 NRF1 (NFE2L1) directly targets the GABARAPL1 promoter after proteasome inhibition; NRF1-mediated GABARAPL1 induction is required for clearance of ubiquitinated proteins via aggrephagy; NRF1 knockdown reduces p62 phosphorylation at Ser403 and impairs p62-positive puncta formation with ULK1 and TBK1. Genome-wide transcriptome analysis, ChIP-qPCR, luciferase reporter assay, NRF1 knockdown, immunofluorescence Scientific reports High 37658135
2023 vIRF-1 (HHV-8 viral protein) binds directly to GABARAPL1 preferentially (over other ATG8 family members) in infected cells via an LIR-independent mechanism; NIX promotes vIRF-1-GABARAPL1 interaction and vIRF-1 oligomerization; GABARAPL1-deficient cells show substantially impaired mitophagy and reduced HHV-8 productive replication; specific residues in both vIRF-1 and GABARAPL1 are required for mutual interaction. Co-immunoprecipitation, mutagenesis of interaction residues, GABARAPL1 knockdown/knockout, mitophagy assay, viral replication assay PLoS pathogens High 37459327
2023 KDM3B (histone lysine demethylase 3B) directly binds to the GABARAPL1 gene promoter and transcriptionally activates GABARAPL1 expression; KDM3B knockout inhibits GABARAPL1 expression and reduces autophagosome formation and autophagic flux in leukemia cells. ChIP-qPCR, luciferase reporter assay, RNA-seq, KDM3B knockout, autophagic flux assay International journal of oncology Medium 37326062
2025 GABARAPL1 is essential for aminoglycoside (AG)-induced hearing loss; targeted deletion of GABARAPL1 in mice prevents AG-induced hair cell death without affecting normal hearing; GABARAP plays a more significant role than GABARAPL1, and their combined deficiency further protects against AG ototoxicity. Targeted mouse GABARAPL1 knockout, double GABARAP/GABARAPL1 knockout, hearing threshold measurement, hair cell survival assay Proceedings of the National Academy of Sciences of the United States of America High 39928869
2026 GABARAPL1 facilitates the interaction between HSP90 and the heme-regulated inhibitor kinase (HRI), which is required for full HRI activation and downstream eIF2α phosphorylation during sodium arsenite stress; GABARAPL1 absence reduces eIF2α phosphorylation and impairs stress granule formation. GABARAPL1 knockout, co-immunoprecipitation of HSP90-HRI, immunoblot for p-eIF2α, stress granule immunofluorescence Scientific reports Medium 41904211
2024 EGFR contains a functional LIR motif (LIR1: FLPV) that preferentially binds GABARAP and GABARAPL1 in vitro; X-ray crystallography shows canonical binding of LIR1 core residues to both hydrophobic pockets of GABARAP, with GABARAP Y49 and L50 dispensable in this case. In vitro LIR-protein binding assay, X-ray crystallography bioRxivpreprint Medium
2024 Deficiency of GABARAPL1 is associated with diastolic dysfunction in diabetic mice; GABARAPL1 functions as the ATG8 partner for STBD1-mediated glycophagy; Gabarapl1 gene delivery reversed cardiomyocyte and cardiac diastolic dysfunction in type 2 diabetic mice and improved diastolic performance in human iPSC-derived cardiac organoids. Gabarapl1 knockout mouse, gene delivery (AAV), cardiac function measurement (echocardiography), human iPSC cardiac organoids, glycogen quantification bioRxivpreprint Medium

Source papers

Stage 0 corpus · 62 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 218 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 137 21893048
2019 Members of the autophagy class III phosphatidylinositol 3-kinase complex I interact with GABARAP and GABARAPL1 via LIR motifs. Autophagy 97 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 90 24879149
2010 GABARAPL1 (GEC1) associates with autophagic vesicles. Autophagy 89 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 76 21620860
2011 GABARAPL1 (GEC1): original or copycat? Autophagy 75 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
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
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 47 21691068
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
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
2023 The transcription factor NRF1 (NFE2L1) activates aggrephagy by inducing p62 and GABARAPL1 after proteasome inhibition to maintain proteostasis. Scientific reports 27 37658135
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
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
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 13 36336129
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
2015 Gabarapl1 mediates androgen-regulated autophagy in prostate cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 11 26050226
2023 The mitophagy receptor NIX induces vIRF-1 oligomerization and interaction with GABARAPL1 for the promotion of HHV-8 reactivation-induced mitophagy. PLoS pathogens 10 37459327
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
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
2024 Poly-l-arginine promotes ferroptosis in asthmatic airway epithelial cells by modulating PBX1/GABARAPL1 axis. International journal of biological macromolecules 3 39645127
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 1 39308299
2024 GABARAPL1 is essential for ACR-induced autophagic cell death of mouse Leydig cells. Ecotoxicology and environmental safety 1 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
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