checksum
6E7012D3041CD043
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FUNCTION Flippase that catalyzes in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates like 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from the lumen to the cytoplasmic leaflet of photoreceptor outer segment disk membranes, where 11-cis-retinylidene-phosphatidylethanolamine is then isomerized to its all-trans isomer and reduced by RDH8 to produce all-trans-retinol. This transport activity ensures that all-trans-retinal generated from photoexcitation and 11-cis-retinal not needed for the regeneration of rhodopsin and cone opsins are effectively cleared from the photoreceptors, therefore preventing their accumulation and the formation of toxic bisretinoid (PubMed:10075733, PubMed:20404325, PubMed:22735453, PubMed:23144455, PubMed:24097981, PubMed:29847635, PubMed:33375396). Displays ATPase activity in vitro in absence of retinal substrate (PubMed:33605212, PubMed:39128720, PubMed:29847635, PubMed:33375396). May display 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 N-retinylidene-phosphatidylethanolamine release (By similarity).CATALYTIC ACTIVITY an N-all-trans-retinylidenephosphatidylethanolamine(out) + ATP + H2O = an N-all-trans-retinylidenephosphatidylethanolamine(in) + ADP + phosphate + H(+)CATALYTIC ACTIVITY ATP + H2O + phospholipidSide 1 = ADP + phosphate + phospholipidSide 2.CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) + ADP + phosphate + H(+)CATALYTIC ACTIVITY N-11-cis-retinylidenephosphatidylethanolamine(out) + ATP + H2O = N-11-cis-retinylidenephosphatidylethanolamine(in) + ADP + phosphate + H(+)CATALYTIC ACTIVITY ATP + H2O = ADP + phosphate + H(+)ACTIVITY REGULATION ATPase activity is decreased by cholesterol and ceramide. Phospholipids translocase activity is highly reduced by berylium fluoride and aluminum floride. N-ethylmaleimide inhibits phospholipid translocase activity.BIOPHYSICOCHEMICAL PROPERTIES Localized to the rim and incisures of rod outer segments disks.TISSUE SPECIFICITY Retinal-specific. Seems to be exclusively found in the rims of rod photoreceptor cells.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).PTM 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.PTM N-glycosylated.PTM Phosphorylation is independent of light exposure and modulates ATPase activity.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the ABC transporter superfamily. ABCA family.SEQUENCE CAUTION Extended N-terminus.ONLINE INFORMATION Database for mutations in ABC proteins
databaseName
UniProt
dbId
49428
description
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recommendedName: fullName evidence="59"Retinal-specific phospholipid-transporting ATPase ABCA4 ecNumber evidence="39"7.6.2.1 alternativeName: ATP-binding cassette sub-family A member 4 alternativeName: RIM ABC transporter shortName: RIM proteinv shortName: RmP alternativeName: Retinal-specific ATP-binding cassette transporter alternativeName: Stargardt disease protein
displayName
UniProt:P78363 ABCA4
identifier
P78363
isSequenceChanged
false
keyword
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3D-structure
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Age-related macular degeneration
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ATP-binding
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Cell projection
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Cone-rod dystrophy
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Cytoplasmic vesicle
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Disease variant
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Disulfide bond
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Endoplasmic reticulum
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Glycoprotein
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Hydrolase
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Membrane
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Nucleotide-binding
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Phosphoprotein
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Proteomics identification
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Reference proteome
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Repeat
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Retinitis pigmentosa
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Sensory transduction
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Stargardt disease
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Translocase
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Transmembrane
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Transmembrane helix
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Transport
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Vision
moleculeType
Protein
schemaClass
ReferenceGeneProduct
secondaryIdentifier
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ABCA4_HUMAN
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O15112
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O60438
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O60915
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Q0QD48
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Q4LE31
sequenceLength
2273
stId
uniprot:P78363