RBP3 explained

Retinol-binding protein 3, interstitial (RBP3), also known as interphotoreceptor retinoid-binding protein (IRBP), is a protein that in humans is encoded by the RBP3 gene.^[1] RBP3 orthologs^[2] have been identified in most eutherians except tenrecs and armadillos. A horizontal gene transfer from bacteria has been proposed to explain the evolution of the eye in chordates.^[3]

Function

The inter-photoreceptor retinoid-binding protein is a large glycoprotein known to bind retinoids and found primarily in the interphotoreceptor matrix of the retina between the retinal pigment epithelium (RPE) and the photoreceptor cells. It is thought to transport retinoids between the RPE and the photoreceptors, a critical role in the visual process.^{[4] [5]}

Gene

The human IRBP gene is approximately 9.5 kbp in length and consists of four exons separated by three introns. The introns are 1.6-1.9 kbp long. The gene is transcribed by photoreceptor and retinoblastoma cells into an approximately 4.3-kilobase mRNA that is translated and processed into a glycosylated protein of 135,000 Da.

Structure

The amino acid sequence of human IRBP can be divided into four contiguous homology domains with 33-38% identity, suggesting a series of gene duplication events. In the gene, the boundaries of these domains are not defined by exon-intron junctions, as might have been expected. The first three homology domains and part of the fourth are all encoded by the first large exon, which is 3,180 base pairs long. The remainder of the fourth domain is encoded in the last three exons, which are 191, 143, and approximately 740 base pairs long, respectively.^[1]

Application

The rbp3 gene is commonly used in animals as a nuclear DNA phylogenetic marker.^[2] The exon 1 has first been used in a pioneer study to provide evidence for monophyly of Chiroptera.^[6] Then, it has been used to infer the phylogeny of placental mammal orders,^{[7] [8]} and of the major clades of Rodentia,^[9] Macroscelidea,^[10] and Primates.^[11] RBP3 is also useful at lower taxonomic levels, e.g., in muroid rodents^[12] and Malagasy primates,^[13] at the phylogeography level in Geomys and Apodemus rodents,^{[14] [15]} and even for carnivora species identification purposes.^[16]

Note that the RBP3 intron 1 has also been used to investigate the platyrrhine primates phylogenetics.^[17]

Further reading

• Fong SL, Fong WB, Morris TA, Kedzie KM, Bridges CD . Characterization and comparative structural features of the gene for human interstitial retinol-binding protein . The Journal of Biological Chemistry . 265 . 7 . 3648–53 . Mar 1990 . 10.1016/S0021-9258(19)39642-5 . 2303470 . free .
• Albini A, Toffenetti J, Zhu Z, Chader GJ, Noonan DM . Hypomethylation of the interphotoreceptor retinoid-binding protein (IRBP) promotor and first exon is linked to expression of the gene . Nucleic Acids Research . 18 . 17 . 5181–7 . Sep 1990 . 2402443 . 332140 . 10.1093/nar/18.17.5181 .
• Liou GI, Ma DP, Yang YW, Geng L, Zhu C, Baehr W . Human interstitial retinoid-binding protein. Gene structure and primary structure . The Journal of Biological Chemistry . 264 . 14 . 8200–6 . May 1989 . 10.1016/S0021-9258(18)83169-6 . 2542268 . free .
• Si JS, Borst DE, Redmond TM, Nickerson JM . Cloning of cDNAs encoding human interphotoreceptor retinoid-binding protein (IRBP) and comparison with bovine IRBP sequences . Gene . 80 . 1 . 99–108 . Aug 1989 . 2792773 . 10.1016/0378-1119(89)90254-0 . 34897302 .
• Nakamura Y, Lathrop M, Bragg T, Leppert M, O'Connell P, Jones C, Lalouel JM, White R . An extended genetic linkage map of markers for human chromosome 10 . Genomics . 3 . 4 . 389–92 . Nov 1988 . 2907505 . 10.1016/0888-7543(88)90133-4 .
• Fong SL, Bridges CD . Internal quadruplication in the structure of human interstitial retinol-binding protein deduced from its cloned cDNA . The Journal of Biological Chemistry . 263 . 30 . 15330–4 . Oct 1988 . 10.1016/S0021-9258(19)37592-1 . 3170584 . free .
• Liou GI, Fong SL, Gosden J, van Tuinen P, Ledbetter DH, Christie S, Rout D, Bhattacharya S, Cook RG, Li Y . Human interstitial retinol-binding protein (IRBP): cloning, partial sequence, and chromosomal localization . Somatic Cell and Molecular Genetics . 13 . 4 . 315–23 . Jul 1987 . 3455009 . 10.1007/BF01534925 . 20206120 .
• Fong SL, Cook RG, Alvarez RA, Liou GI, Landers RA, Bridges CD . N-terminal sequence homologies in interstitial retinol-binding proteins from 10 vertebrate species . FEBS Letters . 205 . 2 . 309–12 . Sep 1986 . 3743780 . 10.1016/0014-5793(86)80918-8 . 45787370 . free .
• Redmond TM, Wiggert B, Robey FA, Chader GJ . Interspecies conservation of structure of interphotoreceptor retinoid-binding protein. Similarities and differences as adjudged by peptide mapping and N-terminal sequencing . The Biochemical Journal . 240 . 1 . 19–26 . Nov 1986 . 3827838 . 1147370 . 10.1042/bj2400019.
• Chen Y, Houghton LA, Brenna JT, Noy N . Docosahexaenoic acid modulates the interactions of the interphotoreceptor retinoid-binding protein with 11-cis-retinal . The Journal of Biological Chemistry . 271 . 34 . 20507–15 . Aug 1996 . 8702792 . 10.1074/jbc.271.34.20507 . free .
• Shaw NS, Noy N . Interphotoreceptor retinoid-binding protein contains three retinoid binding sites . Experimental Eye Research . 72 . 2 . 183–90 . Feb 2001 . 11161734 . 10.1006/exer.2000.0945 .
• Foltz DR, Nye JS . Hyperphosphorylation and association with RBP of the intracellular domain of Notch1 . Biochemical and Biophysical Research Communications . 286 . 3 . 484–92 . Aug 2001 . 11511084 . 10.1006/bbrc.2001.5421 .
• Howard OM, Dong HF, Su SB, Caspi RR, Chen X, Plotz P, Oppenheim JJ . Autoantigens signal through chemokine receptors: uveitis antigens induce CXCR3- and CXCR5-expressing lymphocytes and immature dendritic cells to migrate . Blood . 105 . 11 . 4207–14 . Jun 2005 . 15713799 . 1895027 . 10.1182/blood-2004-07-2697 .

External links

• GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview
• Web site: Overview of the coding DNA and protein sequence alignments of the RBP3 marker . OrthoMaM – a biological database of orthologous mammalian markers . .

Notes and References

1. Web site: Entrez Gene: RBP3 retinol binding protein 3, interstitial.
2. Web site: OrthoMaM phylogenetic marker: RBP3 gene, exon 1.
3. Kalluraya . Chinmay A. . Weitzel . Alexander J. . Tsu . Brian V. . Daugherty . Matthew D. . 2023-04-18 . Bacterial origin of a key innovation in the evolution of the vertebrate eye . Proceedings of the National Academy of Sciences . en . 120 . 16 . e2214815120 . 10.1073/pnas.2214815120 . 37036996 . 10120077 . 0027-8424. free . 2023PNAS..12014815K .
4. Pennisi E. 10 Apr 2023. An ancient gene stolen from bacteria set the stage for human sight. Science. 10.1126/science.adi2029. 11 Apr 2023.
5. Kusakabe TG, Takimoto N, Jin M, Tsuda M. Oct 2009. Evolution and the origin of the visual retinoid cycle in vertebrates. Philosophical Transactions B. 364. 1531. 2897–2910. 10.1098/rstb.2009.0043. 19720652 . 2781855.
6. Stanhope MJ, Czelusniak J, Si JS, Nickerson J, Goodman M . A molecular perspective on mammalian evolution from the gene encoding interphotoreceptor retinoid binding protein, with convincing evidence for bat monophyly . Molecular Phylogenetics and Evolution . 1 . 2 . 148–60 . Jun 1992 . 1342928 . 10.1016/1055-7903(92)90026-D .
7. Stanhope MJ, Smith MR, Waddell VG, Porter CA, Shivji MS, Goodman M . Mammalian evolution and the interphotoreceptor retinoid binding protein (IRBP) gene: convincing evidence for several superordinal clades . Journal of Molecular Evolution . 43 . 2 . 83–92 . Aug 1996 . 8660440 . 10.1007/BF02337352 . 1996JMolE..43...83S . 25865281 .
8. Madsen O, Scally M, Douady CJ, Kao DJ, DeBry RW, Adkins R, Amrine HM, Stanhope MJ, de Jong WW, Springer MS . Parallel adaptive radiations in two major clades of placental mammals . Nature . 409 . 6820 . 610–4 . Feb 2001 . 11214318 . 10.1038/35054544 . 4398233 .
9. Huchon D, Madsen O, Sibbald MJ, Ament K, Stanhope MJ, Catzeflis F, de Jong WW, Douzery EJ . Rodent phylogeny and a timescale for the evolution of Glires: evidence from an extensive taxon sampling using three nuclear genes . Molecular Biology and Evolution . 19 . 7 . 1053–65 . Jul 2002 . 12082125 . 10.1093/oxfordjournals.molbev.a004164 . free .
10. Douady CJ, Catzeflis F, Raman J, Springer MS, Stanhope MJ . The Sahara as a vicariant agent, and the role of Miocene climatic events, in the diversification of the mammalian order Macroscelidea (elephant shrews) . Proceedings of the National Academy of Sciences of the United States of America . 100 . 14 . 8325–30 . Jul 2003 . 12821774 . 166228 . 10.1073/pnas.0832467100 . free . 2003PNAS..100.8325D .
11. Poux C, Douzery EJ . Primate phylogeny, evolutionary rate variations, and divergence times: a contribution from the nuclear gene IRBP . American Journal of Physical Anthropology . 124 . 1 . 01–16 . May 2004 . 15085543 . 10.1002/ajpa.10322 .
12. Jansa SA, Weksler M . Phylogeny of muroid rodents: relationships within and among major lineages as determined by IRBP gene sequences . Molecular Phylogenetics and Evolution . 31 . 1 . 256–76 . Apr 2004 . 15019624 . 10.1016/j.ympev.2003.07.002 .
13. Horvath JE, Weisrock DW, Embry SL, Fiorentino I, Balhoff JP, Kappeler P, Wray GA, Willard HF, Yoder AD . Development and application of a phylogenomic toolkit: resolving the evolutionary history of Madagascar's lemurs . Genome Research . 18 . 3 . 489–99 . Mar 2008 . 18245770 . 2259113 . 10.1101/gr.7265208 .
14. Genoways HH, Hamilton MJ, Bell DM, Chambers RR, Bradley RD . 2008 . Hybrid zones, genetic isolation, and systematics of pocket gophers (genus Geomys) in Nebraska . J. Mammal. . 89 . 4. 826–836 . 10.1644/07-mamm-a-408.1. free .
15. Tomozawa M, Suzuki H . A trend of central versus peripheral structuring in mitochondrial and nuclear gene sequences of the Japanese wood mouse, Apodemus speciosus . Zoological Science . 25 . 3 . 273–85 . Mar 2008 . 18393564 . 10.2108/zsj.25.273 . 38824060 .
16. Oliveira R, Castro D, Godinho R, Luikart G, Alves PC . Species identification using a small nuclear gene: application to sympatric wild carnivores from South-western Europe . Conserv. Genet. . 11. 3. 1023–1032. June 2009 . 10.1007/s10592-009-9947-4 . 21422211 .
17. Schneider H, Sampaio I, Harada ML, Barroso CM, Schneider MP, Czelusniak J, Goodman M . Molecular phylogeny of the New World monkeys (Platyrrhini, primates) based on two unlinked nuclear genes: IRBP intron 1 and epsilon-globin sequences . American Journal of Physical Anthropology . 100 . 2 . 153–79 . Jun 1996 . 8771309 . 10.1002/(SICI)1096-8644(199606)100:2<153::AID-AJPA1>3.0.CO;2-Z .