Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Retinal stimulates ATP hydrolysis by purified and reconstituted ABCR, the photoreceptor-specific ATP-binding cassette transporter responsible for Stargardt disease.
Interaction of extracellular domain 2 of the human retina-specific ATP-binding cassette transporter (ABCA4) with all-trans-retinal.
ABCA4 is an N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer.
-
Reconstitution directly establishes inward transport of NRPE and PE; free retinol is not transported.
"ABCA4 functions as a novel N-retinylidene-PE and PE importer translocating these substrates from the lumen to the cytoplasmic side of photoreceptor disc membranes"
Retinoid binding properties of nucleotide binding domain 1 of the Stargardt disease-associated ATP binding cassette (ABC) transporter, ABCA4.
Differential phospholipid substrates and directional transport by ATP-binding cassette proteins ABCA1, ABCA7, and ABCA4 and disease-causing mutants.
-
ABCA4 transports PE inward, unlike outward ABCA1/ABCA7 transport.
"In contrast, ABCA4 transported phosphatidylethanolamine in the reverse direction."
Correlating the Expression and Functional Activity of ABCA4 Disease Variants With the Phenotype of Patients With Stargardt Disease.
-
Wild-type protein localizes to vesicle-like structures with some ER staining in transfected cells.
"WT ABCA4 showed a punctate staining pattern characteristic of intracellular vesicle-like structures containing calnexin with some evidence of ER reticular staining."
Functional Characterization of ABCA4 Missense Variants Linked to Stargardt Macular Degeneration.
-
Full-length variant assays examine the retinal-PE adduct rather than free retinal alone.
"ABCA4 immobilized on an immunoaffinity matrix was treated with ATR in the presence of PE to generate N-Ret-PE."
Molecular structures of the eukaryotic retinal importer ABCA4.
-
Cryo-EM resolves two ATP molecules bound to the hydrolysis-deficient human transporter.
"The final model contains 2 ATP molecules, 8 lipid molecules, and 1920 residues."
Structural and functional characterization of the nucleotide-binding domains of ABCA4 and their role in Stargardt disease.
-
Wild-type ABCA4 has basal ATPase activity, abolished by the double Walker-B glutamate substitution.
"The basal ATPase activity of WT ABCA4 exhibited Michaelis–Menten kinetics while the EQ double mutant was devoid of activity"
A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy.
The photoreceptor rim protein is an ABC transporter encoded by the gene for recessive Stargardt's disease (ABCR).
Retinitis pigmentosa caused by a homozygous mutation in the Stargardt disease gene ABCR.
ABCA4 mediates atRAL transport
The canonical retinoid cycle in rods (twilight vision)
Defective ABCA4 does not transport NRPE from disc membranes
ABC-family proteins mediated transport
The effect of lipid environment and retinoids on the ATPase activity of ABCR, the photoreceptor ABC transporter responsible for Stargardt macular dystrophy.
ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11-cis-retinal.
-
ABCA4 also transports the 11-cis retinal-PE adduct; subsequent isomerization is chemical and reduction is performed by RDH.
"ABCA4 can transport N-11-cis-retinylidene-phosphatidylethanolamine (PE), the Schiff-base conjugate of 11-cis-retinal and PE, from the lumen to the cytoplasmic leaflet of disk membranes."
Expression of ABCA4 in the retinal pigment epithelium and its implications for Stargardt macular degeneration.
Cell-autonomous lipid-handling defects in Stargardt iPSC-derived retinal pigment epithelium cells.
Falcon/Edison Scientific ABCA4 literature research report, 2026-09-25
N-retinylidene-phosphatidylethanolamine is the preferred retinoid substrate for the photoreceptor-specific ABC transporter ABCA4 (ABCR).
-
Full-length ABCA4 preferentially binds NRPE, but a smaller amount of free retinal can bind; retinol does not bind.
"No binding of all-trans-retinol to ABCA4 was observed."
Retinal-phospholipid Schiff-base conjugates and their interaction with ABCA4, the ABC transporter associated with Stargardt disease.
Virus-like particles as robust tools for functional assessment: Deciphering the pathogenicity of ABCA4 genetic variants of uncertain significance.
-
Human full-length ABCA4 expressed in insect-derived VLPs retains basal and retinal/PE-stimulated ATP hydrolysis; the assay does not directly measure transbilayer transport.
"we subtracted the ATPase activity of the negative control VLPs from that of the ABCA4-VLP."
Structural basis of substrate recognition and translocation by human ABCA4.
-
Human ABCA4 structures resolve NRPE recognition and an ATP-bound closed conformation, with ATPase assays testing relevant sites.
"In the ATP-bound state, the two TMDs display a closed
conformation, which precludes the substrate binding."
Cryo-EM structures of the ABCA4 importer reveal mechanisms underlying substrate binding and Stargardt disease.
-
Human ABCA4 substrate-site variants alter ATP-dependent NRPE transport as well as binding and ATPase activity.
"The ATP-dependent transport of N-Ret-PE across membranes was carried out as previously described18."
Stargardt macular dystrophy and therapeutic approaches.
-
A clinical review synthesizes ABCA4 retinopathy, variant interpretation and therapeutic approaches.
"The aim of this review is to describe the phenotypic and genotypic characteristics, imaging findings, natural history and pathogenesis of the disease."
The ATP-binding cassette transporter ABCA4: structural and functional properties and role in retinal disease.
-
The 2010 review summarizes a proposed NRPE-clearance mechanism and explicitly calls for a direct transport assay.
"Creation of a transport assay is critical for verification of the proposed substrates and determination of the direction of transport for ABCA4."
Emerging Therapeutic Approaches and Genetic Insights in Stargardt Disease: A Comprehensive Review.
Updates on Emerging Interventions for Autosomal Recessive ABCA4-Associated Stargardt Disease.
-
A review discusses emerging gene, small-molecule and stem-cell interventions for ABCA4-associated Stargardt disease.
"In the present article, we review the most
recent updates in clinical trials targeting the management of STGD1, including
gene therapy, small molecule therapy, and stem cell therapy."