ArticleBiochemistry2011
Posttranslational modifications of the photoreceptor-specific ABC transporter ABCA4.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Deciphering the impact of ABCA4 genetic variants of unknown significance in inherited retinal disease through computational and functional approaches.Advances in protein chemistry and structural biology · 2025Review
- A Proximity Complementation Assay to Identify Small Molecules That Enhance the Traffic of ABCA4 Misfolding Variants.International journal of molecular sciences · 2024Article
- Mass spectrometry-based retina proteomics.Mass spectrometry reviews · 2023Review
- Cryo-EM structures of the ABCA4 importer reveal mechanisms underlying substrate binding and Stargardt disease.Nature communications · 2021Article
- Therapy Approaches for Stargardt Disease.Biomolecules · 2021Review
- The GARP Domain of the Rod CNG Channel's β1-Subunit Contains Distinct Sites for Outer Segment Targeting and Connecting to the Photoreceptor Disk Rim.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Article
- Strategies to gain novel Alzheimer's disease diagnostics and therapeutics using modulators of ABCA transporters.Free neuropathology · 2021Article
- Functional Genomics of the Retina to Elucidate its Construction and Deconstruction.International journal of molecular sciences · 2019Review
- The selective estrogen receptor modulator raloxifene mitigates the effect of all-The Journal of biological chemistry · 2019Article
- An AAV Dual Vector Strategy Ameliorates the Stargardt Phenotype in AdultHuman gene therapy · 2019Article
- Identification of novel pathogenicBioscience reports · 2019Article
- Conversion of all-The Journal of biological chemistry · 2018Article
- Protein misfolding and the pathogenesis of ABCA4-associated retinal degenerations.Human molecular genetics · 2015Article
- Reliable determination of site-specific in vivo protein N-glycosylation based on collision-induced MS/MS and chromatographic retention time.Journal of the American Society for Mass Spectrometry · 2014Article
- Expression, purification and structural properties of ABC transporter ABCA4 and its individual domains.Protein expression and purification · 2014Article
- ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11-cis-retinal.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Inherent instability of the retinitis pigmentosa P23H mutant opsin.The Journal of biological chemistry · 2014Article
- Chemistry of the retinoid (visual) cycle.Chemical reviews · 2014Review
- Structural and functional analysis of the native peripherin-ROM1 complex isolated from photoreceptor cells.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
ABCA4 is a photoreceptor-specific ATP-binding cassette transporter implicated in the clearance of all-trans-retinal produced in the retina during light perception. Multiple mutations in this protein have been linked to Stargardt disease and other visual disorders. Here we report the first systematic study of posttranslational modifications in native ABCA4 purified from bovine rod outer segments. Seven N-glycosylation sites were detected in exocytoplasmic domains 1 and 2 by mass spectrometry, confirming the topological model of ABCA4 proposed previously. The modifying oligosaccharides were relatively short and homogeneous, predominantly representing a high-mannose type of N-glycosylation. Five phosphorylation sites were detected in cytoplasmic domain 1, with four of them located in the linker "regulatory-like" region conserved among ABCA subfamily members. Contrary to published results, phosphorylation of ABCA4 was found to be independent of light. Using human ABCA4 mutants heterologously expressed in mammalian cells, we showed that the Stargardt disease-associated alanine mutation in the phosphorylation site at position 901 led to protein misfolding and degradation. Furthermore, replacing the S1317 phosphorylation site reduced the basal ATPase activity of ABCA4, whereas an alanine mutation in either the S1185 or T1313 phosphorylation site resulted in a significant decrease in the all-trans-retinal-stimulated ATPase activity without affecting the basal activity, protein expression, or localization. In agreement with this observation, partial dephosphorylation of native bovine ABCA4 led to reduction of both basal and stimulated ATPase activity. Thus, we present the first evidence that phosphorylation of ABCA4 can regulate its function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.