InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ABCA4

Summary

InnateDB Protein

IDBP-100360.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ABCA4

Protein Name

ATP-binding cassette, sub-family A (ABC1), member 4

Synonyms

ABC10; ABCR; ARMD2; CORD3; FFM; RMP; RP19; STGD; STGD1;

Species

Homo sapiens

Ensembl Protein

ENSP00000359245

InnateDB Gene

IDBG-100358 (ABCA4)

Protein Structure

UniProt Annotation

Function

In the visual cycle, acts as an inward-directed retinoid flipase, retinoid substrates imported by ABCA4 from the extracellular or intradiscal (rod) membrane surfaces to the cytoplasmic membrane surface are all-trans-retinaldehyde (ATR) and N-retinyl-phosphatidyl-ethanolamine (NR-PE). Once transported to the cytoplasmic surface, ATR is reduced to vitamin A by trans- retinol dehydrogenase (tRDH) and then transferred to the retinal pigment epithelium (RPE) where it is converted to 11-cis-retinal. May play a role in photoresponse, removing ATR/NR-PE from the extracellular photoreceptor surfaces during bleach recovery. {ECO:0000269PubMed:10075733}.

Subcellular Localization

Membrane {ECO:0000269PubMed:10075733}; Multi-pass membrane protein {ECO:0000269PubMed:10075733}. Note=Localized to outer segment disk edges of rods and cones, with around one million copies/photoreceptor.

Disease Associations

Stargardt disease 1 (STGD1) [MIM:248200]: 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. {ECO:0000269PubMed:10090887, ECO:0000269PubMed:10206579, ECO:0000269PubMed:10612508, ECO:0000269PubMed:10634594, ECO:0000269PubMed:10711710, ECO:0000269PubMed:10746567, ECO:0000269PubMed:10958763, ECO:0000269PubMed:11328725, ECO:0000269PubMed:11385708, ECO:0000269PubMed:11527935, ECO:0000269PubMed:11594993, ECO:0000269PubMed:18977788, ECO:0000269PubMed:9054934, ECO:0000269PubMed:9490294, ECO:0000269PubMed:9503029, ECO:0000269PubMed:9781034, ECO:0000269PubMed:9973280}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:11379881, ECO:0000269PubMed:11385708, ECO:0000269PubMed:9781034}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:19028736, ECO:0000269PubMed:9295268}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.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. {ECO:0000269PubMed:10958761, ECO:0000269PubMed:11385708, ECO:0000269PubMed:11527935}. Note=The disease is caused by mutations affecting the gene represented in this entry.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. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Retinal-specific. Seems to be exclusively found in the rims of rod photoreceptor cells.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 2 experimentally validated interaction(s) in this database.

Experimentally validated
Total	2 [view]
Protein-Protein	1 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004012	phospholipid-translocating ATPase activity
GO:0005215	transporter activity
GO:0005524	ATP binding
GO:0005548	phospholipid transporter activity
GO:0016887	ATPase activity
GO:0042626	ATPase activity, coupled to transmembrane movement of substances

Biological Process

GO:0001523	retinoid metabolic process
GO:0006200	ATP catabolic process
GO:0006649	phospholipid transfer to membrane
GO:0006810	transport
GO:0007601	visual perception
GO:0007603	phototransduction, visible light
GO:0045332	phospholipid translocation
GO:0045494	photoreceptor cell maintenance
GO:0055085	transmembrane transport

Cellular Component

GO:0005887	integral component of plasma membrane
GO:0016020	membrane
GO:0097381	photoreceptor disc membrane

Protein Structure and Domains

PDB ID

InterPro

IPR003439 ABC transporter-like
IPR003593 AAA+ ATPase domain
IPR005951 Rim ABC transporter
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00005

PRINTS

PIRSF

SMART

SM00382

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P78363