ABCA4 Membrane Protein Introduction

Introduction of ABCA4

ABCA4 encoded by ABCA4 gene is a member of the superfamily of ATP-binding cassette (ABC) transporters which transport various molecules across extra- and intracellular membranes. There are seven subfamilies in ABC superfamily named as ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White, respectively. ABCA4 protein belongs to ABC1 subfamily which consists of two transmembrane domains, two large extracellular domains, and two internal nucleotide binding domains.

Function of ABCA4 Membrane Protein

ABCA4 is a transmembrane protein located in rod and cone outer segment disc membranes. It functions as an inward-directed retinoid flippase in the visual cycle and transports retinoid substrates that are all all-trans-retinaldehyde (ATR) and N-retinyl-phosphatidyl-ethanolamine (NR-PE) from the extracellular or intradiscal (rod) membrane surfaces to the cytoplasmic membrane surface. Then ATR on the cytoplasmic membrane surface converts into vitamin A by trans-retinol dehydrogenase (tRDH) and then transforms into 11-cis-retinal on the retinal pigment epithelium (RPE). Hence, ABCA4 exerts a key role in clearing ATR/NR-PE from the extracellular photoreceptor surfaces during bleach recovery. ABCA4 knockout mouse may display a delayed dark adaptation and accumulate all-trans-retinaldehyde following light exposure. And variants in ABCA4 are associated with autosomal-recessive disease - Stargardt macular dystrophy (STGD). In addition, mutations in ABCA4 are also linked to other eye diseases such as cone-rod dystrophy type 3, fundus flavimaculatus, early-onset severe retinal dystrophy, and macular degeneration age-related 2.

Fig.1 Diagram showing the reactions involved in the clearance of 11-cis- and all-trans-retinal from photoreceptor disk membranes. (Quazi, 2014)

Application of ABCA4 Membrane Protein in Literature

1. Runhart E.H., et al. The common ABCA4 variant p.Asn1868Ile shows nonpenetrance and variable expression of Stargardt disease when present in trans with severe variants. Invest Ophthalmol Vis Sci. 2018, 59(8): 3220-3231. PubMed ID: 29971439
   
   

   The study shows a common ABCA4 variant p.Asn1868Ile in a lot of nonpenetrance and variable expression of Stargardt disease (STGD1) cases.

2. Fujinami K., et al. Detailed genetic characteristics of an international large cohort of patients with Stargardt disease. ProgStar study report 8. Br J Ophthalmol. 2018. PubMed ID: 29925512
   
   

   The study shows 211 likely pathogenic variants are detected in the total 345 participants with a clinical diagnosis of STGD1. And among those, 50 variants are first reported. Moreover, there are significant differences in allele frequency of 9 variants between 4 nations.

3. Garces F., et al. Correlating the Expression and functional activity of ABCA4 disease variants with the phenotype of patients with Stargardt disease. Investigative Ophthalmology & Visual Science. 2018, 59(6): 2305-2315. PubMed ID: 29847635
   
   

   The study shows that the expression and residual activity of ABCA4 mutants are responsible for the phenotype of patients with Stargardt disease.

4. Zernant J., et al. Extremely hypomorphic and severe deep intronic variants in the ABCA4 locus result in varying Stargardt disease phenotypes. Cold Spring Harbor Molecular Case Studies. 2018, 4(4). PubMed ID: 29848554
   
   

   The study reveals three non-coding pathogenic variants of ABCA4 in Stargardt disease patients of European descent. And the non-coding pathogenic variants can be determined by integrated clinical and genetic outcomes.

5. Stavrenia K., et al. Mutation spectrum of the ABCA4 gene in a Greek cohort with Stargardt Disease: identification of novel mutations and evidence of three prevalent mutated alleles. Journal of Ophthalmology. 2018, 5706142. PubMed ID: 29854428
   
   

   The authors analyze the ABCA4 mutations of 59 patients with Stargardt disease and identify 6 novel and potentially pathogenic mutations in ABCA4.

ABCA4 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-ABCA4 antibody development services.

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Reference

1. Quazi F and Molday R S. (2014). ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11-cis-retinal. Proc Natl Acad Sci U S A. 111(13), 5024-9.

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