Search results for ABCA4

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Protein (5 results from a total of 5)

Identifier: R-HSA-1457539
Species: Homo sapiens
Compartment: photoreceptor disc membrane
Primary external reference: UniProt: ABCA4: P78363
Identifier: R-HSA-2466821
Species: Homo sapiens
Compartment: photoreceptor disc membrane
Primary external reference: UniProt: ABCA4: P78363
Identifier: R-HSA-2466850
Species: Homo sapiens
Compartment: photoreceptor disc membrane
Primary external reference: UniProt: ABCA4: P78363
Identifier: R-HSA-2466780
Species: Homo sapiens
Compartment: photoreceptor disc membrane
Primary external reference: UniProt: ABCA4: P78363
Identifier: R-HSA-2466827
Species: Homo sapiens
Compartment: photoreceptor disc membrane
Primary external reference: UniProt: ABCA4: P78363

Set (1 results from a total of 1)

Identifier: R-HSA-2466752
Species: Homo sapiens
Compartment: photoreceptor disc membrane

Reaction (6 results from a total of 6)

Identifier: R-HSA-1467466
Species: Homo sapiens
Compartment: photoreceptor outer segment membrane, cytosol
Rhodopsin (RHO) is localised to both the disc membrane and the plasma membrane of rod outer segments (ROS). All-trans-retinal (atRAL) released from rhodopsin during the bleaching process, needs to translocate to the cytosol for reduction to all-trans-retinol (atROL) via all-trans-retinol dehydrogenases. Although atRAL can diffuse through membranes unaided, there exists an ABC transporter on disc membranes which may facilitate the transport of excess atRAL. Retinal-specific ATP-binding cassette transporter (ABCA4, ABCR) is the only ABC transporter which mediates the transport of retinoids (Biswas & Biswas 2000). Studies using bovine ABCA4 demonstrates atRAL transport (Sun et al. 1999). Human ABCR was found to be identical to the ABC transporter linked to Stargardt's disease type 1 (STGD1, MIM:248200), a cause of macular degeneration in childhood (Nasonkin et al. 1998).
Identifier: R-HSA-2466802
Species: Homo sapiens
Compartment: photoreceptor disc membrane, cytosol, photoreceptor outer segment membrane
ATP-binding cassette protein A4 (ABCA4, ABCR), expressed exclusively in retinal photoreceptors, is thought to be involved in the clearance of toxic by-products of the retinoid cycle. Defects in ABCA4 cause a diverse range of human diseases. One such disease is Stargardt's disease type 1 (STGD1, MIM:248200) (Allikmets et al. 1997), an autosomal recessive form of juvenile macular degeneration leading to progressive irreversible loss of central vision and delayed dark adaptation. STGD1 was first identified by Stargardt in 1909 (Stargardt, Arch. Klin. Exp. Ophthal. 71: 534-549, 1909), has an approximate prevalence of 1 in 10,000 (see reviews Paskowitz et al. 2006, Walia & Fishman 2009) and is usually diagnosed within the first two decades of life.

The cause of retinal cell death is believed to be due to the accumulation of an age-related pigment called lipofuscin, which contains toxic by-products of the visual cycle (see review Sparrow et al. 2009). One prevelant toxic by-product, diretinoid-pyridinium-ethanolamine (A2E), is formed from condensation of two molecules of all-trans-retinal and one molecule of phosphatidylethanolamine (PE). Its precursors (atRAL and N-retinyl-phosphatidylethanolamine (NRPE)) are found in ocular tissues from Stargardt patients (Rozet et al. 1998). Another toxic intermediate is atRAL itself, the precursor to A2E. Studies in Abca4- and Rdh-deficient mice reveal atRAL's involvement in acute light-induced retinopathy (Maeda et al. 2009a, b).

Common mutations leading to STGD1 are A1038V, G1961E (Lewis et al. 1999), G863A (or delG863, not described here; Maugeri et al. 1999), R943Q (Allikmets et al. 1997) and T1428M (thought to be prevelant in 8% of the Japanese population; Kuroiwa et al. 1999).
Identifier: R-HSA-2466749
Species: Homo sapiens
Compartment: cytosol, photoreceptor disc membrane, photoreceptor outer segment membrane
Bovine studies (Beharry et al. 2004) have indicated NRPE to be the preferred substrate for ABCA4 (ABCR, rim protein, RmP) (Azarian et al. 1998), which acts as an inward-directed retinoid flippase and facilitates the transfer of NRPE to the cytoplasmic side of the disc membrane. This transfer is essential to avoid build up of potentially toxic retinoid intermediates which are implicated in many retinal degenerative diseases (see review Tsybovsky et al. 2010). Defective ABCA4 cannot perform this function leading to impaired vision and blindness disorders such as Stargardt disease (MIM:248200).
Identifier: R-HSA-2466718
Species: Homo sapiens
Compartment: cytosol, photoreceptor outer segment membrane
Once NRPE is "flipped" to the cytoplasmic side of disc membranes by the ABC transporter ABCA4, it can dissociate to all-trans-retinal (atRAL) and phosphatidylethanolamine (PE). atRAL is thus released to re-enter the retinoid cycle to reform the visual chromophore 11-cis-retinal (11cRAL) (Tsybovsky et al. 2010).
Identifier: R-HSA-2464810
Species: Homo sapiens
Compartment: cytosol, photoreceptor outer segment membrane
The majority of all-trans-retinal (atRAL) simply diffuses across membranes into the cytosol. Experiments performed with mice rods demonstrate that atRAL diffusion is independent of assisted transport by ABCA4 (Mata et al. 2000, Blakeley et al. 2011).
Identifier: R-HSA-2466846
Species: Homo sapiens
Compartment: photoreceptor outer segment membrane, photoreceptor disc membrane
In the disc membranes of photoreceptor outer segments, all-trans-retinal (atRAL) can spontaneously and reversibly react with phosphatidiylethanolamine (PE, cephalin; a phospholipid found in in membranes) to form a Schiff base product, N-retinylidene-phosphatidylethanolamine (NRPE) (Poincelot et al. 1969, Parish et al. 1998, Mata et al. 2000). Then, either NRPE is "flipped" over to the cytoplasmic side of disc membranes by ABCA4 where it can dissociate (thus releasing atRAL to re-enter the retinoid cycle) or it can condense with another atRAL to form a toxic diretinal compound. The route taken is determined by whether a functional ABCA4 protein is present or not.

Icon (1 results from a total of 1)

Species: Homo sapiens
Curator: Bijay Jassal
Designer: Cristoffer Sevilla
ABCA4 icon
Retinal-specific phospholipid-transporting ATPase ABCA4
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