| RLBP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | RLBP1 , CRALBP, retinaldehyde binding protein 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 180090 MGI: 97930 HomoloGene: 68046 GeneCards: RLBP1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Retinaldehyde-binding protein 1 (RLBP1) also known as cellular retinaldehyde-binding protein (CRALBP) is a 36-kD water-soluble protein that in humans is encoded by the RLBP1 gene. [5] [6] [7]
Cellular retinol binding protein (CRBP) was first discovered in 1973 from lung tissues by Bashor et al. [8] There have been three cellular retinol binding protein categories discovered; Cellular retinol-binding protein, cellular retinoic acid-binding protein and cellular retinaldehyde-binding protein(CRALBP). [8] [9] [10] CRALBP was first discovered in 1977, after it was purified from retina and retinal pigment epithelial cells. [10] [11]
The cellular retinaldehyde-binding protein transports 11-cis-retinal (also known as 11-cis-retinaldehyde) as its physiological ligands. It plays a critical role as an 11-cis-retinal acceptor which facilitates the enzymatic isomerization of all 11-trans-retinal to 11-cis-retinal, in the isomerization of the rod and cones of the visual cycle. [12] [13]
CRALBP is not just found in retina and retinal pigment epithelial cells, but also expressed in other cell types. It is majorly found in the iris, cornea, ciliary epithelium, Muller cells, the pineal gland and oligodendrocytes of the optic nerve and brain. This protein is also found in other tissues than the aforementioned ones, however its function in cells not related to the eyes are not yet known [14]
When a visual pigment molecule in photoreceptors of mammalian rod and cone cells are triggered by photons of light, the pigment molecule is unable to detect an ensuing photon of light. All the retinal molecules in the chromophore of the visual pigment molecule, exist in the 11-trans-retinal state after stimulation by photons. RLBP1 helps in converting the 11-trans-retinal to the light sensitive 11-cis retinal. This process is a part of the visual cycle, which involves the expulsion of all 11-trans-retinal containing chromophores out of photoreceptors, and subsequent conversion to the 11-cis-retinal state in retinal pigment epithelial cells, for both rod and cone cells. The 11-cis chromophore is then signalled back into photoreceptor cells, where it undergoes fusion with a free opsin molecule to regenerate the visual pigment. [15] [16] [13]
The RLBP1 gene is located on human chromosome 15, specifically on 15q26. This gene was formerly believed to have 8 exons and 7 introns. [5] [17] However, Vogel et al. demonstrated that there are actually 8 introns on that chromosome. [18] A gene element, upstream of the previously thought exon 1 was originally thought to be an enhancer. In reality, this assumed enhancer is the main promoter for this gene. The newly discovered intron 1 lies within and just near the end of the promoter region of RLBP1 gene. [18]
Mutations of RLBP1 include several diseases associated with vision. All of these are autosomal recessive including Bothnia dystrophy, retinitis punctata albescens, retinitis pigmentosa, Newfoundland rod-cone dystrophy and fundus albipunctatus. The characteristics of the associated diseases vary with age, severity and rate of progression. These all have similar qualities such as, photoreceptor deterioration and slower dark adaptation, ultimately leading to visual impairment, often leading to complete blindness. [14]
People suffering from Bothnia dystrophy have a homozygous C to T base pair substitution in exon 7 of the RLBP1 gene. This leads to a missense mutation from Arginine to Tryptophan at the 234 position of the RLBP1. [19]
Katsanis et al. showed that a homozygous alteration from Arginine to Glutamine amino acid expression, at the 150 position on RLBP1, brings about the onset of retinitis punctata albescens and or fundus albipunctatus. [20]
Rhodopsin, also known as visual purple, is a protein encoded by the RHO gene and a G-protein-coupled receptor (GPCR). It is the opsin of the rod cells in the retina and a light-sensitive receptor protein that triggers visual phototransduction in rods. Rhodopsin mediates dim light vision and thus is extremely sensitive to light. When rhodopsin is exposed to light, it immediately photobleaches. In humans, it is regenerated fully in about 30 minutes, after which the rods are more sensitive. Defects in the rhodopsin gene cause eye diseases such as retinitis pigmentosa and congenital stationary night blindness.
Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision. As peripheral vision worsens, people may experience "tunnel vision". Complete blindness is uncommon. Onset of symptoms is generally gradual and often begins in childhood.
Retinal is a polyene chromophore. Retinal, bound to proteins called opsins, is the chemical basis of visual phototransduction, the light-detection stage of visual perception (vision).
Retinoic acid (used simplified here for all-trans-retinoic acid) is a metabolite of vitamin A1 (all-trans-retinol) that mediates the functions of vitamin A1 required for growth and development. All-trans-retinoic acid is required in chordate animals, which includes all higher animals from fish to humans. During early embryonic development, all-trans-retinoic acid generated in a specific region of the embryo helps determine position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages.
The visual cycle is a process in the retina that replenishes the molecule retinal for its use in vision. Retinal is the chromophore of most visual opsins, meaning it captures the photons to begin the phototransduction cascade. When the photon is absorbed, the 11-cis retinal photoisomerizes into all-trans retinal as it is ejected from the opsin protein. Each molecule of retinal must travel from the photoreceptor cell to the RPE and back in order to be refreshed and combined with another opsin. This closed enzymatic pathway of 11-cis retinal is sometimes called Wald's visual cycle after George Wald (1906–1997), who received the Nobel Prize in 1967 for his work towards its discovery.
The photoreceptor cell-specific nuclear receptor (PNR), also known as NR2E3, is a protein that in humans is encoded by the NR2E3 gene. PNR is a member of the nuclear receptor super family of intracellular transcription factors.
In enzymology, a retinol dehydrogenase (RDH) (EC 1.1.1.105) is an enzyme that catalyzes the chemical reaction
RPE-retinal G protein-coupled receptor also known as RGR-opsin is a protein that in humans is encoded by the RGR gene. RGR-opsin is a member of the rhodopsin-like receptor subfamily of GPCR. Like other opsins which bind retinaldehyde, it contains a conserved lysine residue in the seventh transmembrane domain. RGR-opsin comes in different isoforms produced by alternative splicing.
ATP-binding cassette, sub-family A (ABC1), member 4, also known as ABCA4 or ABCR, is a protein which in humans is encoded by the ABCA4 gene.
Peripherin-2 is a protein, that in humans is encoded by the PRPH2 gene. Peripherin-2 is found in the rod and cone cells of the retina of the eye. Defects in this protein result in one form of retinitis pigmentosa, an incurable blindness.
Bestrophin-1 (Best1) is a protein that, in humans, is encoded by the BEST1 gene.
Retinal pigment epithelium-specific 65 kDa protein, also known as retinoid isomerohydrolase, is an enzyme of the vertebrate visual cycle that is encoded in humans by the RPE65 gene. RPE65 is expressed in the retinal pigment epithelium and is responsible for the conversion of all-trans-retinyl esters to 11-cis-retinol during phototransduction. 11-cis-retinol is then used in visual pigment regeneration in photoreceptor cells. RPE65 belongs to the carotenoid oxygenase family of enzymes.
Cone-rod homeobox protein is a protein that in humans is encoded by the CRX gene.
11-cis retinol dehydrogenase is an enzyme that in humans is encoded by the RDH5 gene.
Proto-oncogene tyrosine-protein kinase MER is an enzyme that in humans is encoded by the MERTK gene.
Retinol dehydrogenase 12 is an enzyme that in humans is encoded by the RDH12 gene.
Lecithin retinol acyltransferase is an enzyme that in humans is encoded by the LRAT gene.
Retinal gene therapy holds a promise in treating different forms of non-inherited and inherited blindness.
NADP-retinol dehydrogenase (EC 1.1.1.300, all-trans retinal reductase, all-trans-retinol dehydrogenase, NADP(H)-dependent retinol dehydrogenase/reductase, RDH11, RDH12, RDH13, RDH14, retinol dehydrogenase 12, retinol dehydrogenase 14, retinol dehydrogenase (NADP+), RalR1, PSDR1) is an enzyme with systematic name retinol:NADP+ oxidoreductase. This enzyme catalyses the following chemical reaction
11-cis-retinol dehydrogenase (EC 1.1.1.315, RDH5 (gene)) is an enzyme with systematic name 11-cis-retinol:NAD+ oxidoreductase. This enzyme catalyses the following chemical reaction
