ABCA4
Domain
The second extracellular domain (ECD2, aa 1395-1680) undergoes conformational change in response to its specific interaction with its substrate all-trans-retinal (PubMed:20404325). Nucleotide binding domain 1 (NBD1, aa 854-1375) binds preferentially and with high affinity with the 11-cis retinal (PubMed:23144455).
Function
Flippase that catalyzes in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates like the 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine from the lumen to the cytoplasmic leaflet of photoreceptor outer segment disk membranes, where N-cis-retinylidene-phosphatidylethanolamine (N-cis-R-PE) is then isomerized to its all-trans isomer (N-trans-R-PE) and reduced by RDH8 to produce all-trans-retinol (all-trans-rol) and therefore prevents the accumulation of excess of 11-cis-retinal and its schiff-base conjugate and the formation of toxic bisretinoid (PubMed:10075733, PubMed:20404325, PubMed:22735453, PubMed:23144455, PubMed:24097981, PubMed:29847635, PubMed:33375396). May display both ATPase and GTPase activity that is strongly influenced by the lipid environment and the presence of retinoid compounds (PubMed:22735453). Binds the unprotonated form of N-retinylidene-phosphatidylethanolamine with high affinity in the absence of ATP, and ATP binding and hydrolysis induce a protein conformational change that causes the dissociation of N-retinylidene-phosphatidylethanolamine (By similarity).
Involvement in disease
Stargardt disease 1
STGD1
A common hereditary macular degeneration. It is characterized by decreased central vision, atrophy of the macula and underlying retinal pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina.
None
The disease is caused by variants affecting the gene represented in this entry.
Fundus flavimaculatus
FFM
Autosomal recessive retinal disorder very similar to Stargardt disease. In contrast to Stargardt disease, FFM is characterized by later onset and slowly progressive course.
None
The disease is caused by variants affecting the gene represented in this entry.
Macular degeneration, age-related, 2
ARMD2
A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Cone-rod dystrophy 3
CORD3
An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors.
None
The disease is caused by variants affecting the gene represented in this entry.
Retinitis pigmentosa 19
RP19
A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP19 is characterized by choroidal atrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Proteolytic cleavage by trypsin leads to a 120-kDa N-terminal fragment and a 115-kDa C-terminal fragment that are linked through disulfide bonds.
N-glycosylated.
Phosphorylation is independent of light exposure and modulates ATPase activity.
Sequence Similarities
Belongs to the ABC transporter superfamily. ABCA family.
Tissue Specificity
Retinal-specific. Seems to be exclusively found in the rims of rod photoreceptor cells.
Cellular localization
- Membrane
- Multi-pass membrane protein
- Endoplasmic reticulum
- Cytoplasmic vesicle
- Cell projection
- Cilium
- Photoreceptor outer segment
- Localized to the rim and incisures of rod outer segments disks.
Alternative names
ABCR, ABCA4, Retinal-specific phospholipid-transporting ATPase ABCA4, ATP-binding cassette sub-family A member 4, RIM ABC transporter, Retinal-specific ATP-binding cassette transporter, Stargardt disease protein, RIM proteinv, RmP