Disease relevance of RCVRN

• Cancer-associated retinopathy (CAR) is an ocular manifestation of a paraneoplastic syndrome whereby immunological reactions toward recoverin (Rec), a retina-specific Ca(2+) binding protein, and its aberrant expression in tumor cells lead to the retinal degeneration [1].
• Cancer-associated retinopathy (CAR), a paraneoplastic syndrome, is characterized by the degeneration of retinal photoreceptors under conditions where the tumor and its metastases have not invaded the eye [2].
• Cancer-associated retinopathy (CAR) is a rare form of retinal degeneration that occurs in association with certain forms of cancer [3].
• We examined the expression of recoverin in human lung cancer cell lines by reverse transcription polymerase chain reaction (PCR), Northern blotting and Western immunoblotting [4].
• To identify potential cis-elements that may be involved in understanding the mechanisms that determine the cell-specific expression of recoverin in retinal and cancerous cells, the promoter region of the human recoverin gene was studied in cultured human Y79 retinoblastoma cells [5].

High impact information on RCVRN

• Cancer-associated retinopathy (CAR syndrome) with antibodies reacting with retinal, optic-nerve, and cancer cells [6].
• Recoverin has a relative molecular mass of 23,000 (M[r] 23K), and contains an amino-terminal myristoyl group (or related acyl group) and four EF hands [7].
• One such protein is recoverin, a calcium sensor in retinal rod cells, which controls the lifetime of photoexcited rhodopsin by inhibiting rhodopsin kinase [7].
• The conservation of the myristoyl binding site and two swivels in recoverin homologues from yeast to humans indicates that calcium-myristoyl switches are ancient devices for controlling calcium-sensitive processes [7].
• The binding of two Ca2+ ions to recoverin leads to its translocation from the cytosol to the disc membrane [7].

Chemical compound and disease context of RCVRN

• Tamoxifen side effects, age-related macular degeneration (AMD) or cancer associated retinopathy (CAR) [8]?

Biological context of RCVRN

• The first eight residues of recoverin at the N terminus are solvent-exposed, enabling the N-terminal myristoyl group to interact with target membranes, and Ca(2+) is bound at the second and third EF-hands of the protein [9].
• Residues of recoverin that contact RK25 are highly conserved, suggesting a similar target binding site structure in all neuronal calcium sensor proteins [9].
• Hybridization to the somatic hybrid cell line DNAs localized the recoverin gene to chromosome 17 [10].
• Recoverin is a calcium-binding protein that may be involved in phototransduction in mammalian retinal photoreceptors, and is considered to be a candidate gene for retinitis pigmentosa [10].
• Nucleotide sequence analysis suggests that the CAR antigen shows approximately 90% homology to the published amino acid sequence of bovine recoverin [3].

Anatomical context of RCVRN

• Aberrantly expressed recoverin is functionally associated with G-protein-coupled receptor kinases in cancer cell lines [1].
• A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy [2].
• We suggest the term "cancer-retina antigens" for this kind of proteins like recoverin that are solely expressed in retina and tumor tissues and evoke antibodies and/or T cells in patients with cancer [11].
• Recoverin belongs to the superfamily of EF-hand Ca2+-binding proteins and operates as a Ca2+-sensor in vertebrate photoreceptor cells, where it regulates the activity of rhodopsin kinase GRK1 in a Ca2+-dependent manner [12].
• In addition, cultured cells from the biopsy tissue expressed recoverin, as demonstrated by reverse transcription-PCR using RNA extracted from the cells [13].

Associations of RCVRN with chemical compounds

• Structural Basis for Calcium-induced Inhibition of Rhodopsin Kinase by Recoverin [9].
• Finally, our studies also revealed two separate and previously unreported effects of adenine nucleotides on the recoverin-rhodopsin kinase binding [14].
• Recoverin is a recently discovered 26 kDa calcium-binding protein, which activates guanylate cyclase in retinal photoreceptors when the intracellular concentration of free calcium drops upon photoexcitation [15].
• We conclude from our results that Alexa647 bound to cysteine 38 can monitor the conformational transition in recoverin that is under control of the myristoyl group [12].
• That recoverin binds calcium was confirmed with calcium-45 and by observing calcium-induced changes in its tryptophan fluorescence [16].

Physical interactions of RCVRN

• Recoverin is a 23 kDa myristoylated Ca2+-binding protein that inhibits rhodopsin kinase [14].
• Our analyses confirmed that Ca2+ is required for recoverin to bind RK [14].
• Recoverin is a calcium-binding protein identified as an autoantigen in a paraneoplastic degenerative disease of the human retina known as cancer-associated retinopathy (CAR) [17].

Regulatory relationships of RCVRN

• In the presence of calcium, rhodopsin kinase (GRK1) is inhibited by the photoreceptor-specific CSP recoverin through direct binding [18].
• Rhodopsin phosphorylation in bovine ROS was significantly promoted by the addition of anti-recoverin antibody [19].
• Immunofluorescence staining showed that thymoma cells also expressed recoverin [20].

Other interactions of RCVRN

• Immunocytochemistry revealed that immunoreactivities toward Rec within the cancer cells were almost identical to those toward GRKs and caveolin-1 [1].
• GCAP3 contains two domains with the EF-hand motifs arranged in a tandem array similar to GCAP2 and members of the recoverin subfamily of Ca2+-binding proteins [21].
• This study was undertaken to develop the recoverin locus into a polymorphic marker for future linkage studies on retinitis pigmentosa families [10].
• A homology model of CIB based upon calcineurin B and recoverin indicated a conserved hydrophobic pocket within the C-terminal EF-hand motifs of CIB as a potential integrin-binding site [22].
• In peripheral retina at 15.4 weeks to 1 month after birth, displaced cones in the nerve fiber layer are positive for TULP1, recoverin, and blue cone opsin [23].

Analytical, diagnostic and therapeutic context of RCVRN

• To elucidate functional roles of the aberrantly expression in cancer cells, we performed immunoprecipitation using anti-human Rec mAb [1].
• Recoverin was further localized to 17p12-p13 by fluorescence in situ hybridization [10].
• We have used surface plasmon resonance to investigate the influences of Ca2+, myristoylation, and adenine nucleotides on the recoverin-rhodopsin kinase interaction [14].
• A possible application of recoverin as a potential target for immunotherapy of cancer is discussed [11].
• In addition, two of the proteins, recoverin and guanylate cyclase activating protein (GCAP), appear to be involved in separate degenerative diseases of the retina that arise in humans and in animal models of human disease [24].

References