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. Nucleotide binding domain 1 (NBD1, aa 854-1375) binds preferentially and with high affinity with the 11-cis retinal.
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:10412977, PubMed:10852960, PubMed:22735453). Displays both ATPase and GTPase activity that is strongly influenced by the lipid environment and the presence of retinoid compounds (By similarity). 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).
Post-translational modifications
N-glycosylated.
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.
Phosphorylation is independent of light exposure and modulates ATPase activity.
Sequence Similarities
Belongs to the ABC transporter superfamily. ABCA family.
Tissue Specificity
Retinal-specific (PubMed:9202155). Seems to be exclusively found in the rims of rod photoreceptor cells.
Cellular localization
- Membrane
- Multi-pass membrane protein
- Endoplasmic reticulum
- 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, RIM protein, RmP