RPE-retinal G protein-coupled receptor also known as RGR-opsin is a
protein that in humans is encoded by the RGRgene.[5][6] 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.[7][8] RGR-opsin comes in different isoforms produced by alternative splicing.[6]
Function
RGR-opsin preferentially binds all-trans-retinal,[8] which is the dominant form in the dark adapted retina, upon light exposure it is isomerized to 11-cis-retinal.[9] Therefore, RGR-opsin presumably acts as a photoisomerase to convert all-trans-
retinal to 11-cis-retinal, similar to
retinochrome in
invertebrates. 11-cis-retinal is isomerized back within rhodopsin and the iodopsins in the
rods and
cones of the retina. RGR-opsin is exclusively expressed in tissue close to the rods and cones, the
retinal pigment epithelium (RPE) and
Müller cells.[7]
Phylogeny
The RGR-opsins are restricted to the
echinoderms, the
hemichordates the craniates.[10] The
craniates are the
taxon that contains
mammals and with them humans. The RGR-opsins are one of the seven subgroups of the chromopsins. The other groups are the
peropsins, the
retinochromes, the nemopsins, the astropsins, the varropsins, and the gluopsins.[10] The chromopsins are one of three subgroups of the tetraopsins (also known as RGR/Go or Group 4 opsins). The other groups are the
neuropsins and the Go-opsins. The tetraopsins are one of the five major groups of the animal
opsins, also known as type 2 opsins). The other groups are the ciliary opsins (c-opsins, cilopsins), the rhabdomeric opsins (r-opsins, rhabopsins), the xenopsins, and the nessopsins. Four of these subclades occur in
Bilateria (all but the nessopsins).[10][11] However, the bilaterian clades constitute a
paraphyletic taxon without the opsins from the
cnidarians.[10][11][12][13]
The phylogenetic relationship of the RGR-opsins to the other opsins
Phylogenetic reconstruction of the opsins. The outgroup contains other
G protein-coupled receptors. The frame highlights the tetraopsins, which are expanded in the next image.
Phylogenetic reconstruction of the tetraopsins. The outgroup contains other G protein-coupled receptors including the other opsins. The frame highlights the chromopsins, which are expanded in the next image.
Phylogenetic reconstruction of the chromopsins. The outgroup contains other G protein-coupled receptors including the other opsins. The frame highlights the RGR-opsins.
In the
phylogeny above, Each
clade contains sequences from opsins and other G protein-coupled receptors. The number of sequences and two pie charts are shown next to the clade. The first pie chart shows the percentage of a certain
amino acid at the position in the sequences corresponding to position 296 in cattle rhodopsin. The amino acids are color-coded. The colors are red for
lysine (K), purple for
glutamic acid (E), orange for
arginine (R), dark and mid-gray for other amino acids, and light gray for sequences that have no data at that position. The second pie chart gives the taxon composition for each clade, green stands for
craniates, dark green for
cephalochordates, mid green for
echinoderms, brown for
nematodes, pale pink for
annelids, dark blue for
arthropods, light blue for
mollusks, and purple for
cnidarians. The branches to the clades have pie charts, which give support values for the branches. The values are from right to left SH-aLRT/aBayes/UFBoot. The branches are considered supported when SH-aLRT ≥ 80%, aBayes ≥ 0.95, and UFBoot ≥ 95%. If a support value is above its threshold the pie chart is black otherwise gray.[10]
Clinical significance
RGR-opsin may be associated with autosomal recessive and autosomal dominant
retinitis pigmentosa (arRP and adRP, respectively).[14][6]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Chen XN, Korenberg JR, Jiang M, Shen D, Fong HK (Jun 1996). "Localization of the human RGR opsin gene to chromosome 10q23". Human Genetics. 97 (6): 720–2.
doi:
10.1007/BF02346179.
PMID8641686.
S2CID6086858.
^
abJiang M, Pandey S, Fong HK (Dec 1993). "An opsin homologue in the retina and pigment epithelium". Investigative Ophthalmology & Visual Science. 34 (13): 3669–78.
PMID8258527.
^
abShen D, Jiang M, Hao W, Tao L, Salazar M, Fong HK (Nov 1994). "A human opsin-related gene that encodes a retinaldehyde-binding protein". Biochemistry. 33 (44): 13117–25.
doi:
10.1021/bi00248a022.
PMID7947717.
^Morimura H, Saindelle-Ribeaudeau F, Berson EL, Dryja TP (Dec 1999). "Mutations in RGR, encoding a light-sensitive opsin homologue, in patients with retinitis pigmentosa". Nature Genetics. 23 (4): 393–4.
doi:
10.1038/70496.
PMID10581022.
S2CID35176366.
^Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J,
Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8.
Bibcode:
2005Natur.437.1173R.
doi:
10.1038/nature04209.
PMID16189514.
S2CID4427026.
Further reading
Jiang M, Shen D, Tao L, Pandey S, Heller K, Fong HK (Apr 1995). "Alternative splicing in human retinal mRNA transcripts of an opsin-related protein". Experimental Eye Research. 60 (4): 401–6.
doi:
10.1016/S0014-4835(05)80096-X.
PMID7789419.
Shen D, Jiang M, Hao W, Tao L, Salazar M, Fong HK (Nov 1994). "A human opsin-related gene that encodes a retinaldehyde-binding protein". Biochemistry. 33 (44): 13117–25.
doi:
10.1021/bi00248a022.
PMID7947717.
Lin MY, Kochounian H, Moore RE, Lee TD, Rao N, Fong HK (2007). "Deposition of exon-skipping splice isoform of human retinal G protein-coupled receptor from retinal pigment epithelium into Bruch's membrane". Molecular Vision. 13: 1203–14.
PMID17679941.