ABCA4
entrez
24
canonical
uniprot
P78363
canonical
ensembl
ENSG00000198691
resolver
ensp
ENSP00000359245
resolver
enst
ENST00000370225
resolver
genesymbol
ABCA4
resolver
genesymbol_syn
ABCR
resolver
hgnc
HGNC:34
resolver
uniprot
O15112
resolver
uniprot
O60438
resolver
uniprot
O60915
resolver
uniprot
Q0QD48
resolver
uniprot
Q4LE31
resolver
uniprot_entry
ABCA4_HUMAN
resolver
uniprot_sec
O15112
resolver
uniprot_sec
O60438
resolver
uniprot_sec
O60915
resolver
uniprot_sec
Q0QD48
resolver
uniprot_sec
Q4LE31
resolver
activity_regulation
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. {ECO:0000269|PubMed:24097981}.
uniprot
proteins
amino_acid_sequence
MGFVRQIQLLLWKNWTLRKRQKIRFVVELVWPLSLFLVLIWLRNANPLYSHHECHFPNKAMPSAGMLPWLQGIFCNVNNPCFQSPTPGESPGIVSNYNNSILARVYRDFQELLMNAPESQHLGRIWTELHILSQFMDTLRTHPERIAGRGIRIRDILKDEETLTLFLIKNIGLSDSVVYLLINSQVRPEQFAHGVPDLALKDIACSEALLERFIIFSQRRGAKTVRYALCSLSQGTLQWIEDTLYANVDFFKLFRVLPTLLDSRSQGINLRSWGGILSDMSPRIQEFIHRPSMQDLLWVTRPLMQNGGPETFTKLMGILSDLLCGYPEGGGSRVLSFNWYEDNNYKAFLGIDSTRKDPIYSYDRRTTSFCNALIQSLESNPLTKIAWRAAKPLLMGKILYTPDSPAARRILKNANSTFEELEHVRKLVKAWEEVGPQIWYFFDNSTQMNMIRDTLGNPTVKDFLNRQLGEEGITAEAILNFLYKGPRESQADDMANFDWRDIFNITDRTLRLVNQYLECLVLDKFESYNDETQLTQRALSLLEENMFWAGVVFPDMYPWTSSLPPHVKYKIRMDIDVVEKTNKIKDRYWDSGPRADPVEDFRYIWGGFAYLQDMVEQGITRSQVQAEAPVGIYLQQMPYPCFVDDSFMIILNRCFPIFMVLAWIYSVSMTVKSIVLEKELRLKETLKNQGVSNAVIWCTWFLDSFSIMSMSIFLLTIFIMHGRILHYSDPFILFLFLLAFSTATIMLCFLLSTFFSKASLAAACSGVIYFTLYLPHILCFAWQDRMTAELKKAVSLLSPVAFGFGTEYLVRFEEQGLGLQWSNIGNSPTEGDEFSFLLSMQMMLLDAAVYGLLAWYLDQVFPGDYGTPLPWYFLLQESYWLGGEGCSTREERALEKTEPLTEETEDPEHPEGIHDSFFEREHPGWVPGVCVKNLVKIFEPCGRPAVDRLNITFYENQITAFLGHNGAGKTTTLSILTGLLPPTSGTVLVGGRDIETSLDAVRQSLGMCPQHNILFHHLTVAEHMLFYAQLKGKSQEEAQLEMEAMLEDTGLHHKRNEEAQDLSGGMQRKLSVAIAFVGDAKVVILDEPTSGVDPYSRRSIWDLLLKYRSGRTIIMSTHHMDEADLLGDRIAIIAQGRLYCSGTPLFLKNCFGTGLYLTLVRKMKNIQSQRKGSEGTCSCSSKGFSTTCPAHVDDLTPEQVLDGDVNELMDVVLHHVPEAKLVECIGQELIFLLPNKNFKHRAYASLFRELEETLADLGLSSFGISDTPLEEIFLKVTEDSDSGPLFAGGAQQKRENVNPRHPCLGPREKAGQTPQDSNVCSPGAPAAHPEGQPPPEPECPGPQLNTGTQLVLQHVQALLVKRFQHTIRSHKDFLAQIVLPATFVFLALMLSIVIPPFGEYPALTLHPWIYGQQYTFFSMDEPGSEQFTVLADVLLNKPGFGNRCLKEGWLPEYPCGNSTPWKTPSVSPNITQLFQKQKWTQVNPSPSCRCSTREKLTMLPECPEGAGGLPPPQRTQRSTEILQDLTDRNISDFLVKTYPALIRSSLKSKFWVNEQRYGGISIGGKLPVVPITGEALVGFLSDLGRIMNVSGGPITREASKEIPDFLKHLETEDNIKVWFNNKGWHALVSFLNVAHNAILRASLPKDRSPEEYGITVISQPLNLTKEQLSEITVLTTSVDAVVAICVIFSMSFVPASFVLYLIQERVNKSKHLQFISGVSPTTYWVTNFLWDIMNYSVSAGLVVGIFIGFQKKAYTSPENLPALVALLLLYGWAVIPMMYPASFLFDVPSTAYVALSCANLFIGINSSAITFILELFENNRTLLRFNAVLRKLLIVFPHFCLGRGLIDLALSQAVTDVYARFGEEHSANPFHWDLIGKNLFAMVVEGVVYFLLTLLVQRHFFLSQWIAEPTKEPIVDEDDDVAEERQRIITGGNKTDILRLHELTKIYPGTSSPAVDRLCVGVRPGECFGLLGVNGAGKTTTFKMLTGDTTVTSGDATVAGKSILTNISEVHQNMGYCPQFDAIDELLTGREHLYLYARLRGVPAEEIEKVANWSIKSLGLTVYADCLAGTYSGGNKRKLSTAIALIGCPPLVLLDEPTTGMDPQARRMLWNVIVSIIREGRAVVLTSHSMEECEALCTRLAIMVKGAFRCMGTIQHLKSKFGDGYIVTMKIKSPKDDLLPDLNPVEQFFQGNFPGSVQRERHYNMLQFQVSSSSLARIFQLLLSHKDSLLIEEYSVTQTTLDQVFVNFAKQQTESHDLPLHPRAAGASRQAQD
uniprot
proteins
disease_involvement
DISEASE: Stargardt disease 1 (STGD1) [MIM:248200]: An autosomal recessive form of Stargardt disease, a retinal degenerative disease characterized by macular dystrophy, progressive bilateral atrophy of the foveal retinal pigment epithelium, and accumulation of fluorescent flecks around the macula and/or in the central and near-peripheral areas of the retina. STGD1 patients typically lose central vision in their first or second decade of life. {ECO:0000269|PubMed:10090887, ECO:0000269|PubMed:10206579, ECO:0000269|PubMed:10612508, ECO:0000269|PubMed:10634594, ECO:0000269|PubMed:10711710, ECO:0000269|PubMed:10746567, ECO:0000269|PubMed:10958763, ECO:0000269|PubMed:11328725, ECO:0000269|PubMed:11385708, ECO:0000269|PubMed:11527935, ECO:0000269|PubMed:11594993, ECO:0000269|PubMed:15192030, ECO:0000269|PubMed:18334942, ECO:0000269|PubMed:18977788, ECO:0000269|PubMed:19028736, ECO:0000269|PubMed:19265867, ECO:0000269|PubMed:20404325, ECO:0000269|PubMed:22735453, ECO:0000269|PubMed:23143460, ECO:0000269|PubMed:23144455, ECO:0000269|PubMed:23419329, ECO:0000269|PubMed:23755871, ECO:0000269|PubMed:24097981, ECO:0000269|PubMed:24444108, ECO:0000269|PubMed:24457364, ECO:0000269|PubMed:25346251, ECO:0000269|PubMed:26780318, ECO:0000269|PubMed:29847635, ECO:0000269|PubMed:33375396, ECO:0000269|PubMed:9054934, ECO:0000269|PubMed:9295268, ECO:0000269|PubMed:9490294, ECO:0000269|PubMed:9503029, ECO:0000269|PubMed:9781034, ECO:0000269|PubMed:9973280}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Fundus flavimaculatus (FFM) [MIM:248200]: Autosomal recessive retinal disorder very similar to Stargardt disease. In contrast to Stargardt disease, FFM is characterized by later onset and slowly progressive course. {ECO:0000269|PubMed:10634594, ECO:0000269|PubMed:11379881, ECO:0000269|PubMed:11385708, ECO:0000269|PubMed:9781034}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Macular degeneration, age-related, 2 (ARMD2) [MIM:153800]: 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. {ECO:0000269|PubMed:9295268}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Cone-rod dystrophy 3 (CORD3) [MIM:604116]: 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. {ECO:0000269|PubMed:10634594, ECO:0000269|PubMed:10958761, ECO:0000269|PubMed:11385708, ECO:0000269|PubMed:11527935, ECO:0000269|PubMed:19028736, ECO:0000269|PubMed:25346251, ECO:0000269|PubMed:26780318}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 19 (RP19) [MIM:601718]: 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. {ECO:0000269|PubMed:10634594, ECO:0000269|PubMed:10958763, ECO:0000269|PubMed:19028736, ECO:0000269|PubMed:25346251, ECO:0000269|PubMed:29847635}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
7.6.2.1
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:F1MWM0, ECO:0000269|PubMed:10075733, ECO:0000269|PubMed:20404325, ECO:0000269|PubMed:22735453, ECO:0000269|PubMed:23144455, ECO:0000269|PubMed:24097981, ECO:0000269|PubMed:29847635, ECO:0000269|PubMed:33375396, ECO:0000269|PubMed:33605212, ECO:0000269|PubMed:39128720}.
uniprot
proteins
mass_dalton
255944
uniprot
proteins
mutagenesis
MUTAGEN 345; /note="Y->A: Loss of N-Ret-PE-stimulated ATPase activity. No effect on basal ATPase activity."; /evidence="ECO:0000269|PubMed:34625547"; MUTAGEN 345; /note="Y->C: Loss of N-Ret-PE-stimulated ATPase activity. No effect on basal ATPase activity. Decreased N-retinylidene-phosphatidylethanolamine flippase activity. Decreased affinity for N-all-trans-retinylidenephosphatidylethanolamine."; /evidence="ECO:0000269|PubMed:34625547"; MUTAGEN 587; /note="R->A: Loss of N-Ret-PE-stimulated ATPase activity. No effect on basal ATPase activity. Decreased N-retinylidene-phosphatidylethanolamine flippase activity. Decreased affinity for N-all-trans-retinylidenephosphatidylethanolamine."; /evidence="ECO:0000269|PubMed:34625547"; MUTAGEN 863; /note="Missing: Reduced retinal-stimulated ATP hydrolysis."; /evidence="ECO:0000269|PubMed:11017087"; MUTAGEN 940; /note="P->R: Decreases 11-cis-Retinal binding affinity by 50%."; /evidence="ECO:0000269|PubMed:23144455"; MUTAGEN 965; /note="N->A: No significant effect on basal ATPase activity. Decreased N-Ret-PE-stimulated ATPase activity."; /evidence="ECO:0000269|PubMed:39128720"; MUTAGEN 965; /note="N->D,K: Decreased N-Ret-PE binding to 50%-63% of wild-type values."; /evidence="ECO:0000269|PubMed:39128720"; MUTAGEN 965; /note="N->D,K: Results in minimal, if any, basal ATPase activity. Loss of N-Ret-PE-stimulated ATPase activity."; /evidence="ECO:0000269|PubMed:39128720"; MUTAGEN 965; /note="N->Q: Decreased basal ATPase activity. Loss of N-Ret-PE-stimulated ATPase activity."; /evidence="ECO:0000269|PubMed:39128720"; MUTAGEN 966; /note="G->D: Abolishes basal and retinal-stimulated ATP hydrolysis."; /evidence="ECO:0000269|PubMed:11017087"; MUTAGEN 969; /note="K->M: Abolishes basal and retinal-stimulated ATP hydrolysis."; /evidence="ECO:0000269|PubMed:11017087"; MUTAGEN 969; /note="K->M: Inhibits ATPase activity; when associated with M-1978. Decreases translocase activity; when associated with M-1978. Does not affect protein subcellular localization in endoplasmic reticulum; when associated with M-1978. Loss of ATP-dependent all-trans-retinal transport; when associated with M-1978. Loss in N-retinylidene-PE transfer activity. Inhibits ATPase activity with increasing retinal concentration. Does not affect N-retinylidene-PE binding. Impairs ATP-dependent release of N-retinylidene-PE. Significantly reduces PE flippase activity."; /evidence="ECO:0000269|PubMed:22735453, ECO:0000269|PubMed:24097981"; MUTAGEN 1087; /note="E->Q: Severely decreased basal ATPase activity and loss of N-Ret-PE-stimulated ATPase activity. Does not affect protein folding; when associated with Q-2096. Loss of basal and N-Ret-PE-stimulated ATPase activity; when associated with Q-2096."; /evidence="ECO:0000269|PubMed:33605212, ECO:0000269|PubMed:39128720"; MUTAGEN 1502; /note="C->R: Moderately decreased protein abundance. Moderately decreased ATPase activity. Moderately decreased phospholipid translocase activity."; /evidence="ECO:0000269|PubMed:24097981"; MUTAGEN 1703; /note="Q->K: Decreased solubility. Loss of cytoplasmic vesicle localization. Severely decreased basal and N-Ret-PE-induced ATPase activity. Decreased N-all-trans-retinylidenephosphatidylethanolamine binding."; /evidence="ECO:0000269|PubMed:33375396"; MUTAGEN 1838; /note="H->R: Severely decreases solubility. Loss of cytoplasmic vesicle localization. Decreases basal ATPase activity below 50%. Severe decrease of N-Ret-PE-induced stimulation in ATPase activity. Decreased N-all-trans-retinylidenephosphatidylethanolamine binding."; /evidence="ECO:0000269|PubMed:33375396"; MUTAGEN 1974; /note="N->D,K,Y: Decreased basal ATPase activity and loss of N-Ret-PE-stimulated ATPase activity."; /evidence="ECO:0000269|PubMed:39128720"; MUTAGEN 1974; /note="N->D: Decreased N-Ret-PE binding to 25% of wild-type values."; /evidence="ECO:0000269|PubMed:39128720"; MUTAGEN 1974; /note="N->S,A,Q: No significant effect on basal ATPase activity. Decreased N-Ret-PE-stimulated ATPase activity."; /evidence="ECO:0000269|PubMed:39128720"; MUTAGEN 1975; /note="G->D: Inhibition of retinal-stimulated ATP hydrolysis."; /evidence="ECO:0000269|PubMed:11017087"; MUTAGEN 1978; /note="K->M: Inhibits ATPase activity; when associated with M-969. Decreases translocase activity; when associated with M-969. Does not affect protein subcellular localization in endoplasmic reticulum; when associated with M-969. Loss of ATP-dependent all-trans-retinal transport; when associated with M-1978. Loss in N-retinylidene-PE transfer activity. Inhibits ATPase activity with increasing retinal concentration. Does not affect ATP-independent N-retinylidene-PE binding. Does not affect ATP-dependent of N-retinylidene-PE release. Significantly reduces PE flippase activity. Inhibition of retinal-stimulated ATP hydrolysis."; /evidence="ECO:0000269|PubMed:11017087, ECO:0000269|PubMed:22735453, ECO:0000269|PubMed:24097981"; MUTAGEN 2096; /note="E->Q: Decreased basal ATPase activity and loss of N-Ret-PE-stimulated ATPase activity. Does not affect protein folding; when associated with Q-1087. Loss of ATPase activity; when associated with Q-1087."; /evidence="ECO:0000269|PubMed:33605212, ECO:0000269|PubMed:39128720"; MUTAGEN 2107; /note="R->P: Highly decreased protein abundance. Highly decreased ATPase activity. Highly decreased phospholipid translocase activity."; /evidence="ECO:0000269|PubMed:24097981"; MUTAGEN 2175; /note="K->A: 2-fold decreased binding affinity for ATP. Loss of ATPase activity."; /evidence="ECO:0000269|PubMed:12962493"; MUTAGEN 2180; /note="P->L: Does not affect protein abundance. Does not affect ATPase activity. Moderately decreased phospholipid translocase activity."; /evidence="ECO:0000269|PubMed:24097981
uniprot
proteins
post_translational_modification
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. {ECO:0000269|PubMed:11320094}.; PTM: N-glycosylated. {ECO:0000269|PubMed:11320094}.; PTM: Phosphorylation is independent of light exposure and modulates ATPase activity. {ECO:0000250|UniProtKB:F1MWM0}.
uniprot
proteins
protein_family
ABC transporter superfamily
uniprot
proteins
protein_family
ABCA family
uniprot
proteins
pubmed
10075733
uniprot
proteins
pubmed
10090887
uniprot
proteins
pubmed
10206579
uniprot
proteins
pubmed
10612508
uniprot
proteins
pubmed
10634594
uniprot
proteins
pubmed
10711710
uniprot
proteins
pubmed
10746567
uniprot
proteins
pubmed
10880298
uniprot
proteins
pubmed
10958761
uniprot
proteins
pubmed
10958763
uniprot
proteins
pubmed
11017087
uniprot
proteins
pubmed
11320094
uniprot
proteins
pubmed
11328725
uniprot
proteins
pubmed
11346402
uniprot
proteins
pubmed
11379881
uniprot
proteins
pubmed
11384574
uniprot
proteins
pubmed
11385708
uniprot
proteins
pubmed
11527935
uniprot
proteins
pubmed
11594993
uniprot
proteins
pubmed
12111378
uniprot
proteins
pubmed
12962493
uniprot
proteins
pubmed
15192030
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17286855
uniprot
proteins
pubmed
18334942
uniprot
proteins
pubmed
18977788
uniprot
proteins
pubmed
19028736
uniprot
proteins
pubmed
19265867
uniprot
proteins
pubmed
20335603
uniprot
proteins
pubmed
20404325
uniprot
proteins
pubmed
22735453
uniprot
proteins
pubmed
23143460
uniprot
proteins
pubmed
23144455
uniprot
proteins
pubmed
23419329
uniprot
proteins
pubmed
23755871
uniprot
proteins
pubmed
24097981
uniprot
proteins
pubmed
24444108
uniprot
proteins
pubmed
24457364
uniprot
proteins
pubmed
25346251
uniprot
proteins
pubmed
26780318
uniprot
proteins
pubmed
29847635
uniprot
proteins
pubmed
30120214
uniprot
proteins
pubmed
31481235
uniprot
proteins
pubmed
33375396
uniprot
proteins
pubmed
33605212
uniprot
proteins
pubmed
34625547
uniprot
proteins
pubmed
39128720
uniprot
proteins
pubmed
9054934
uniprot
proteins
pubmed
9202155
uniprot
proteins
pubmed
9295268
uniprot
proteins
pubmed
9466990
uniprot
proteins
pubmed
9490294
uniprot
proteins
pubmed
9503029
uniprot
proteins
pubmed
9781034
uniprot
proteins
pubmed
9973280
uniprot
proteins
sequence_length
2273
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:10075733}; Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum {ECO:0000269|PubMed:24097981}. Cytoplasmic vesicle {ECO:0000269|PubMed:29847635, ECO:0000269|PubMed:33375396}. Cell projection, cilium, photoreceptor outer segment {ECO:0000250|UniProtKB:F1MWM0}. Note=Localized to the rim and incisures of rod outer segments disks. {ECO:0000250|UniProtKB:F1MWM0}.
uniprot
proteins
transmembrane_region
TRANSMEM 22..42; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 647..667; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 700..720; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 731..751; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 760..780; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 836..856; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1377..1397; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1728..1748; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1760..1780; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1793..1813; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1832..1852; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1874..1894; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins