{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecoverin (RCVRN) is a prototypical intracellular Ca²⁺‐binding protein that plays a central role in the visual transduction cascade. In rod photoreceptors, recoverin regulates the activity of rhodopsin kinase (GRK1) via a Ca²⁺‐dependent myristoyl switch mechanism. Binding of Ca²⁺ to its EF‐hand domains triggers conformational changes and an allosteric cascade that promotes membrane association and the formation of a recoverin–GRK1 complex, thereby delaying rhodopsin phosphorylation and helping to terminate the phototransduction cascade. Structural studies have shown that modifications, such as the oxidation of a conserved cysteine residue (Cys39), lead to significant changes in the protein’s secondary structure, stability, and membrane affinity, ultimately compromising its physiological function. Detailed molecular dynamics simulations and mutagenesis experiments have further delineated how specific residues and conserved clusters in recoverin are critical for maintaining the proper Ca²⁺‐dependent regulatory interactions necessary for vision."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical role in the retina, recoverin is aberrantly expressed in various tumors, where its misexpression is implicated in paraneoplastic syndromes such as cancer-associated retinopathy (CAR). In cancers including small cell lung carcinoma, lung and melanoma tumors, as well as renal cell carcinoma and benign renal oncocytoma, epigenetic alterations—such as promoter demethylation or hypomethylation—facilitate the ectopic production of recoverin. This aberrant expression can trigger an autoimmune response, leading to the formation of anti-recoverin antibodies that interfere with normal recoverin function, promote abnormal rhodopsin phosphorylation, and ultimately induce retinal apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, recoverin’s unique expression profile and its involvement in both visual signaling and paraneoplastic retinopathy render it a promising biomarker and potential therapeutic target. Screening for anti-recoverin antibodies is emerging as a valuable clinical tool in the diagnosis and management of retinal degenerative diseases, such as retinitis pigmentosa, particularly in elderly patients who may also have underlying malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Allan Wiechmann, Eric Howard "}, {"type": "b", "children": [{"type": "t", "text": "Functional analysis of the human recoverin gene promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Eye Res (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1076/ceyr.26.1.25.14249"}], "href": "https://doi.org/10.1076/ceyr.26.1.25.14249"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12789533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12789533"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Aya Torisawa, Daisuke Arinobu, Shuji Tachibanaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Amino acid residues in GRK1/GRK7 responsible for interaction with S-modulin/recoverin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Photochem Photobiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1751-1097.2007.00292.x"}], "href": "https://doi.org/10.1111/j.1751-1097.2007.00292.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18266817"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18266817"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sergei E Permyakov, Evgeni Yu Zernii, Ekaterina L Knyazeva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oxidation mimicking substitution of conservative cysteine in recoverin suppresses its membrane association."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Amino Acids (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00726-011-0843-0"}], "href": "https://doi.org/10.1007/s00726-011-0843-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21344177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21344177"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ramasamy P Kumar, Matthew J Ranaghan, Allen Y Ganjei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal Structure of Recoverin with Calcium Ions Bound to Both Functional EF Hands."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acs.biochem.5b01160"}], "href": "https://doi.org/10.1021/acs.biochem.5b01160"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26584024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26584024"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sergey E Permyakov, Alisa S Vologzhannikova, Ekaterina L Nemashkalova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Experimental Insight into the Structural and Functional Roles of the 'Black' and 'Gray' Clusters in Recoverin, a Calcium Binding Protein with Four EF-Hand Motifs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Molecules (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/molecules24132494"}], "href": "https://doi.org/10.3390/molecules24132494"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31288444"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31288444"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Alberto Borsatto, Valerio Marino, Gianfranco Abrusci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of Membrane and Biological Target on the Structural and Allosteric Properties of Recoverin: A Computational Approach."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms20205009"}], "href": "https://doi.org/10.3390/ijms20205009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31658639"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31658639"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hiroshi Ohguro, Mitsuru Nakazawa "}, {"type": "b", "children": [{"type": "t", "text": "Pathological roles of recoverin in cancer-associated retinopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Exp Med Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-1-4615-0121-3_7"}], "href": "https://doi.org/10.1007/978-1-4615-0121-3_7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12596918"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12596918"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Makoto Kobayashi, Takayuki Ikezoe, Yoshiki Uemura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Establishment of a novel small cell lung carcinoma cell line with specific recoverin expression from a patient with cancer-associated retinopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lung Cancer (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lungcan.2007.01.030"}], "href": "https://doi.org/10.1016/j.lungcan.2007.01.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17374419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17374419"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Alexandr V Bazhin, Charles De Smet, Marina O Golovastova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aberrant demethylation of the recoverin gene is involved in the aberrant expression of recoverin in cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0625.2010.01126.x"}], "href": "https://doi.org/10.1111/j.1600-0625.2010.01126.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20812967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20812967"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Marina O Golovastova, Larisa V Tsoy, Anna V Bocharnikova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The cancer-retina antigen recoverin as a potential biomarker for renal tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-016-4885-5"}], "href": "https://doi.org/10.1007/s13277-016-4885-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26813565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26813565"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Taimu Sato, Koji M Nishiguchi, Kosuke Fujita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum anti-recoverin antibodies is found in elderly patients with retinitis pigmentosa and cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Ophthalmol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/aos.14373"}], "href": "https://doi.org/10.1111/aos.14373"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32043815"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32043815"}]}]}]}