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Retinaldehyde-binding protein 1

RLBP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRLBP1, CRALBP, retinaldehyde binding protein 1
External IDsOMIM: 180090; MGI: 97930; HomoloGene: 68046; GeneCards: RLBP1; OMA:RLBP1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6017

19771

Ensembl

ENSG00000140522

ENSMUSG00000039194

UniProt

P12271

Q9Z275

RefSeq (mRNA)

NM_000326

NM_001173483
NM_020599
NM_001357450

RefSeq (protein)

NP_000317

NP_001166954
NP_065624
NP_001344379

Location (UCSC)Chr 15: 89.21 – 89.22 MbChr 7: 79.02 – 79.04 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Discovery

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]

Function

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]

Tissue distribution

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]

Clinical significance

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]

Gene location

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 and associated diseases

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]

Bothnia dystrophy

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]

Retinitis punctata albescens and fundus albipunctatus

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]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000140522 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039194 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Sparkes RS, Heinzmann C, Goldflam S, Kojis T, Saari JC, Mohandas T, Klisak I, Bateman JB, Crabb JW (January 1992). "Assignment of the gene (RLBP1) for cellular retinaldehyde-binding protein (CRALBP) to human chromosome 15q26 and mouse chromosome 7". Genomics. 12 (1): 58–62. doi:10.1016/0888-7543(92)90406-I. PMID 1733864.
  6. ^ Maw MA, Kennedy B, Knight A, Bridges R, Roth KE, Mani EJ, Mukkadan JK, Nancarrow D, Crabb JW, Denton MJ (October 1997). "Mutation of the gene encoding cellular retinaldehyde-binding protein in autosomal recessive retinitis pigmentosa". Nature Genetics. 17 (2): 198–200. doi:10.1038/ng1097-198. PMID 9326942. S2CID 37723395.
  7. ^ "Entrez Gene: RLBP1 retinaldehyde binding protein 1".
  8. ^ a b Bashor MM, Toft DO, Chytil F (December 1973). "In vitro binding of retinol to rat-tissue components". Proceedings of the National Academy of Sciences of the United States of America. 70 (12): 3483–7. Bibcode:1973PNAS...70.3483B. doi:10.1073/pnas.70.12.3483. PMC 427264. PMID 4519641.
  9. ^ Saari JC, Bredberg L, Garwin GG (November 1982). "Identification of the endogenous retinoids associated with three cellular retinoid-binding proteins from bovine retina and retinal pigment epithelium". The Journal of Biological Chemistry. 257 (22): 13329–33. doi:10.1016/S0021-9258(18)33451-3. PMID 6292186.
  10. ^ a b Futterman S, Saari JC (August 1977). "Occurrence of 11-cis-retinal-binding protein restricted to the retina". Investigative Ophthalmology & Visual Science. 16 (8): 768–71. PMID 560359.
  11. ^ Stubbs GW, Saari JC, Futterman S (September 1979). "11-cis-Retinal-binding protein from bovine retina. Isolation and partial characterization". The Journal of Biological Chemistry. 254 (17): 8529–33. doi:10.1016/S0021-9258(19)86924-7. PMID 468840.
  12. ^ Saari JC, Nawrot M, Kennedy BN, Garwin GG, Hurley JB, Huang J, Possin DE, Crabb JW (March 2001). "Visual cycle impairment in cellular retinaldehyde binding protein (CRALBP) knockout mice results in delayed dark adaptation". Neuron. 29 (3): 739–48. doi:10.1016/S0896-6273(01)00248-3. PMID 11301032.
  13. ^ a b Xue Y, Shen SQ, Jui J, Rupp AC, Byrne LC, Hattar S, Flannery JG, Corbo JC, Kefalov VJ (February 2015). "CRALBP supports the mammalian retinal visual cycle and cone vision". The Journal of Clinical Investigation. 125 (2): 727–38. doi:10.1172/JCI79651. PMC 4319437. PMID 25607845.
  14. ^ a b Kennedy BN, Li C, Ortego J, Coca-Prados M, Sarthy VP, Crabb JW (February 2003). "CRALBP transcriptional regulation in ciliary epithelial, retinal Müller and retinal pigment epithelial cells". Experimental Eye Research. 76 (2): 257–60. doi:10.1016/s0014-4835(02)00308-1. PMID 12565814.
  15. ^ Saari JC (August 2012). "Vitamin A metabolism in rod and cone visual cycles". Annual Review of Nutrition. 32: 125–45. doi:10.1146/annurev-nutr-071811-150748. PMID 22809103.
  16. ^ Wang JS, Kefalov VJ (March 2011). "The cone-specific visual cycle". Progress in Retinal and Eye Research. 30 (2): 115–28. doi:10.1016/j.preteyeres.2010.11.001. PMC 3073571. PMID 21111842.
  17. ^ Intres R, Goldflam S, Cook JR, Crabb JW (October 1994). "Molecular cloning and structural analysis of the human gene encoding cellular retinaldehyde-binding protein". The Journal of Biological Chemistry. 269 (41): 25411–8. doi:10.1016/S0021-9258(18)47265-1. PMID 7929238.
  18. ^ a b Vogel JS, Bullen EC, Teygong CL, Howard EW (August 2007). "Identification of the RLBP1 gene promoter". Investigative Ophthalmology & Visual Science. 48 (8): 3872–7. doi:10.1167/iovs.06-1523. PMID 17652763.
  19. ^ Burstedt MS, Sandgren O, Holmgren G, Forsman-Semb K (April 1999). "Bothnia dystrophy caused by mutations in the cellular retinaldehyde-binding protein gene (RLBP1) on chromosome 15q26". Investigative Ophthalmology & Visual Science. 40 (5): 995–1000. PMID 10102298.
  20. ^ Katsanis N, Shroyer NF, Lewis RA, Cavender JC, Al-Rajhi AA, Jabak M, Lupski JR (June 2001). "Fundus albipunctatus and retinitis punctata albescens in a pedigree with an R150Q mutation in RLBP1". Clinical Genetics. 59 (6): 424–9. doi:10.1034/j.1399-0004.2001.590607.x. PMID 11453974. S2CID 9196078.

Further reading

Quelle: https://en.wikipedia.org/wiki/RLBP1