PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32298085-3 2020 Genes like GUCY2D coding for guanylate cyclase GC-E and GUCA1A coding for the Ca2+-sensor guanylate cyclase-activating protein GCAP1 are critical for a precisely controlled synthesis of the second messenger cGMP. Cyclic GMP 207-211 guanylate cyclase 2D, retinal Homo sapiens 11-17 33539922-4 2021 We found that GMP converts to GDP/GTP in the photoreceptor fraction of the retina ~24-fold faster in wild type mice and ~400-fold faster in rd3 mice than GTP conversion to cGMP by RetGC. Cyclic GMP 172-176 guanylate cyclase 2D, retinal Homo sapiens 180-185 32255808-12 2020 Moreover, HPLC-coupled tandem mass spectrometry (HPLC-MS/MS) was used to analyze the concentration of 3",5"-cyclic guanosine monophosphate (cGMP), suggesting that HPLC-MS/MS is an effective alternative method to evaluate the catalytic activity of wild-type and mutant ROS-GC1. Cyclic GMP 140-144 guanylate cyclase 2D, retinal Homo sapiens 268-275 32173907-7 2020 Depletion of cGMP by deleting retinal guanylate cyclase 1 or inhibition of PKG using chemical inhibitors suppressed the upregulation of RyR2 in CNG channel deficiency. Cyclic GMP 13-17 guanylate cyclase 2D, retinal Homo sapiens 30-57 32025184-13 2019 At high Ca2+ concentrations, GCAP1-D144G stimulated retGC1 in the HEK-293 membrane to significantly increase intracellular cGMP protein concentrations. Cyclic GMP 123-127 guanylate cyclase 2D, retinal Homo sapiens 52-58 27703005-0 2016 The R838S Mutation in Retinal Guanylyl Cyclase 1 (RetGC1) Alters Calcium Sensitivity of cGMP Synthesis in the Retina and Causes Blindness in Transgenic Mice. Cyclic GMP 88-92 guanylate cyclase 2D, retinal Homo sapiens 50-56 29440533-10 2018 In summary, the dysregulation of guanylyl cyclase in RetGC1-linked CORD6 is a "phototransduction disease," which means it is associated with increased free-cGMP and Ca2+ levels in photoreceptors.SIGNIFICANCE STATEMENT In a mouse model expressing human membrane guanylyl cyclase 1 (RetGC1, GUCY2D), a mutation associated with early progressing congenital blindness, cone-rod dystrophy type 6 (CORD6), deregulates calcium-sensitive feedback of phototransduction to the cyclase mediated by guanylyl cyclase activating proteins (GCAPs), which are calcium-sensor proteins. Cyclic GMP 156-160 guanylate cyclase 2D, retinal Homo sapiens 53-59 29440533-10 2018 In summary, the dysregulation of guanylyl cyclase in RetGC1-linked CORD6 is a "phototransduction disease," which means it is associated with increased free-cGMP and Ca2+ levels in photoreceptors.SIGNIFICANCE STATEMENT In a mouse model expressing human membrane guanylyl cyclase 1 (RetGC1, GUCY2D), a mutation associated with early progressing congenital blindness, cone-rod dystrophy type 6 (CORD6), deregulates calcium-sensitive feedback of phototransduction to the cyclase mediated by guanylyl cyclase activating proteins (GCAPs), which are calcium-sensor proteins. Cyclic GMP 156-160 guanylate cyclase 2D, retinal Homo sapiens 67-72 29440533-10 2018 In summary, the dysregulation of guanylyl cyclase in RetGC1-linked CORD6 is a "phototransduction disease," which means it is associated with increased free-cGMP and Ca2+ levels in photoreceptors.SIGNIFICANCE STATEMENT In a mouse model expressing human membrane guanylyl cyclase 1 (RetGC1, GUCY2D), a mutation associated with early progressing congenital blindness, cone-rod dystrophy type 6 (CORD6), deregulates calcium-sensitive feedback of phototransduction to the cyclase mediated by guanylyl cyclase activating proteins (GCAPs), which are calcium-sensor proteins. Cyclic GMP 156-160 guanylate cyclase 2D, retinal Homo sapiens 281-287 29440533-10 2018 In summary, the dysregulation of guanylyl cyclase in RetGC1-linked CORD6 is a "phototransduction disease," which means it is associated with increased free-cGMP and Ca2+ levels in photoreceptors.SIGNIFICANCE STATEMENT In a mouse model expressing human membrane guanylyl cyclase 1 (RetGC1, GUCY2D), a mutation associated with early progressing congenital blindness, cone-rod dystrophy type 6 (CORD6), deregulates calcium-sensitive feedback of phototransduction to the cyclase mediated by guanylyl cyclase activating proteins (GCAPs), which are calcium-sensor proteins. Cyclic GMP 156-160 guanylate cyclase 2D, retinal Homo sapiens 289-295 29440533-10 2018 In summary, the dysregulation of guanylyl cyclase in RetGC1-linked CORD6 is a "phototransduction disease," which means it is associated with increased free-cGMP and Ca2+ levels in photoreceptors.SIGNIFICANCE STATEMENT In a mouse model expressing human membrane guanylyl cyclase 1 (RetGC1, GUCY2D), a mutation associated with early progressing congenital blindness, cone-rod dystrophy type 6 (CORD6), deregulates calcium-sensitive feedback of phototransduction to the cyclase mediated by guanylyl cyclase activating proteins (GCAPs), which are calcium-sensor proteins. Cyclic GMP 156-160 guanylate cyclase 2D, retinal Homo sapiens 392-397 30283299-2 2018 In the light-induced signal cascade, membrane-bound ROS-GC1 restores cGMP levels in the dark in a calcium-dependent manner. Cyclic GMP 69-73 guanylate cyclase 2D, retinal Homo sapiens 52-59 27703005-4 2016 The R838S RetGC1 expression in rod outer segments reduced inhibition of cGMP production in the transgenic mouse retinas at the free calcium concentrations typical for dark-adapted rods. Cyclic GMP 72-76 guanylate cyclase 2D, retinal Homo sapiens 10-16 24860425-5 2014 These mutations, which reduce or abolish the ability of retGC1 to replenish cGMP in photoreceptors, are thought to lead to the biochemical equivalent of chronic light exposure in these cells. Cyclic GMP 76-80 guanylate cyclase 2D, retinal Homo sapiens 56-62 25767116-1 2015 By generating the second messenger cGMP in retinal rods and cones, ROS-GC plays a central role in visual transduction. Cyclic GMP 35-39 guanylate cyclase 2D, retinal Homo sapiens 67-73 25767116-4 2015 Recombinant ROS-GCs synthesized cGMP from GTP at faster rates in the presence of bicarbonate with an ED50 of 27 mM for ROS-GC1 and 39 mM for ROS-GC2. Cyclic GMP 32-36 guanylate cyclase 2D, retinal Homo sapiens 119-126 25767116-9 2015 The findings define a new regulatory mechanism of the ROS-GC system that affects visual transduction and is likely to affect the course of retinal diseases caused by cGMP toxicity. Cyclic GMP 166-170 guanylate cyclase 2D, retinal Homo sapiens 54-60 25256176-3 2014 GUCY2D encodes guanylate cyclase-1 (GC1), a protein expressed in rod and cone photoreceptors that regulates cGMP and Ca(2+) levels within these cells. Cyclic GMP 108-112 guanylate cyclase 2D, retinal Homo sapiens 0-6 24108108-5 2014 Furthermore, RetGC1, a protein linked to LCA that is needed for cGMP synthesis, was dramatically reduced in cones lacking Aipl1. Cyclic GMP 64-68 guanylate cyclase 2D, retinal Homo sapiens 13-19 24616660-9 2014 In contrast, a strong reduction in cGMP synthesis due to an inactive or structurally unstable ROS-GC1 would trigger more severe forms of retinal diseases. Cyclic GMP 35-39 guanylate cyclase 2D, retinal Homo sapiens 94-101 24108108-6 2014 A defect in RetGC1 is supported by our finding that cones lacking Aipl1 exhibited reduced levels of cGMP. Cyclic GMP 100-104 guanylate cyclase 2D, retinal Homo sapiens 12-18 12799385-1 2003 It has been believed that retinal guanylyl cyclase (retGC), a key enzyme in the cGMP recovery to the dark state, is solely activated by guanylyl cyclase-activating proteins (GCAPs) in a Ca2+-sensitive manner. Cyclic GMP 80-84 guanylate cyclase 2D, retinal Homo sapiens 26-50 23328348-3 2013 RETGC-1 functions in phototransduction, synthesising cGMP to open ion channels in photoreceptor outer segments. Cyclic GMP 53-57 guanylate cyclase 2D, retinal Homo sapiens 0-7 23308101-10 2013 This observation is consistent with the report of the role of RD3 in trafficking of GUCYs and gives further support to a common mechanism of photoreceptor degeneration in LCA12 and LCA1, i.e., inability to increase cytoplasmic cGMP concentration in outer segments and thus to recover the dark-state. Cyclic GMP 227-231 guanylate cyclase 2D, retinal Homo sapiens 171-175 19941038-1 2010 Two isoforms of guanylate cyclase, GC1 and GC2 encoded by GUCY2D and GUCY2F, are responsible for the replenishment of cGMP in photoreceptors after exposure to light. Cyclic GMP 118-122 guanylate cyclase 2D, retinal Homo sapiens 58-64 12950265-1 2003 In rod phototransduction, cyclic GMP synthesis by membrane bound guanylate cyclase ROS-GC1 is under Ca(2+)-dependent negative feedback control mediated by guanylate cyclase-activating proteins, GCAP-1 and GCAP-2. Cyclic GMP 26-36 guanylate cyclase 2D, retinal Homo sapiens 83-90 22623665-1 2012 Two calcium-sensitive guanylyl cyclase activating proteins (GCAP1 and GCAP2) activate cGMP synthesis in photoreceptor by retinal membrane guanylyl cyclase isozymes (RetGC1 and RetGC2) to expedite recovery, but calcium-insensitive constitutively active GCAP1 mutants cause photoreceptor degeneration in human patients and transgenic mice. Cyclic GMP 86-90 guanylate cyclase 2D, retinal Homo sapiens 165-171 22623665-3 2012 Furthermore, elimination of RetGC1 but not RetGC2 isozyme reverses abnormal calcium sensitivity of cGMP synthesis and rescues mouse rods in transgenic mice expressing GCAP1 mutants causing photoreceptor disease. Cyclic GMP 99-103 guanylate cyclase 2D, retinal Homo sapiens 28-34 17699662-1 2007 Previous experiments indicate that congenital human retinal degeneration caused by genetic mutations that change the Ca(2+) sensitivity of retinal guanylyl cyclase (retGC) can result from an increase in concentration of free intracellular cGMP and Ca(2+) in the photoreceptors. Cyclic GMP 239-243 guanylate cyclase 2D, retinal Homo sapiens 165-170 17699662-2 2007 To rescue degeneration in transgenic mouse models having either the Y99C or E155G mutations of the retGC modulator guanylyl cyclase-activating protein 1 (GCAP-1), which produce elevated cGMP synthesis in the dark, we used the G90D rhodopsin mutation, which produces constitutive stimulation of cGMP hydrolysis. Cyclic GMP 186-190 guanylate cyclase 2D, retinal Homo sapiens 99-104 17699662-2 2007 To rescue degeneration in transgenic mouse models having either the Y99C or E155G mutations of the retGC modulator guanylyl cyclase-activating protein 1 (GCAP-1), which produce elevated cGMP synthesis in the dark, we used the G90D rhodopsin mutation, which produces constitutive stimulation of cGMP hydrolysis. Cyclic GMP 294-298 guanylate cyclase 2D, retinal Homo sapiens 99-104 12799385-1 2003 It has been believed that retinal guanylyl cyclase (retGC), a key enzyme in the cGMP recovery to the dark state, is solely activated by guanylyl cyclase-activating proteins (GCAPs) in a Ca2+-sensitive manner. Cyclic GMP 80-84 guanylate cyclase 2D, retinal Homo sapiens 52-57 12596930-1 2002 Lowered concentration of Ca2+ ions, resulting from illumination of the photoreceptor cell, is the signal for resynthesis of cGMP by retina-specific guanylyl cyclase (retGC). Cyclic GMP 124-128 guanylate cyclase 2D, retinal Homo sapiens 132-164 12390029-1 2002 In visual transduction, guanylate cyclase-activating proteins (GCAPs) activate the membrane-bound guanylate cyclase 1 (ROS-GC1) to synthesize cGMP under conditions of low cytoplasmic [Ca2+]free. Cyclic GMP 142-146 guanylate cyclase 2D, retinal Homo sapiens 119-126 12596930-1 2002 Lowered concentration of Ca2+ ions, resulting from illumination of the photoreceptor cell, is the signal for resynthesis of cGMP by retina-specific guanylyl cyclase (retGC). Cyclic GMP 124-128 guanylate cyclase 2D, retinal Homo sapiens 166-171 12596936-6 2002 The cone and cone-rod dystrophies that are caused by mutations in RetGC1 or GCAP1 arise from a perturbation of the delicate balance of Ca2+ and cGMP within the photoreceptor cells and it is this disruption that is believed to cause cell death. Cyclic GMP 144-148 guanylate cyclase 2D, retinal Homo sapiens 66-72 11485301-6 2001 Since RGS9-1 also controls the lifetime of transducin-activated PDE through regulating GTPase activity of transducin, this study strongly suggests that RGS9-1 mediates the direct interaction between PDE and retGC systems, and that this ingenious mechanism plays an important role in tuning of cGMP concentration in photoreceptors. Cyclic GMP 293-297 guanylate cyclase 2D, retinal Homo sapiens 207-212 11387342-9 2001 We applied this method, referred to as COSUMAS (contact surfaces by mass spectrometry), to two proteins, retinal guanylyl cyclase 1 (RetGC1) and guanylyl cyclase-activating protein-1 (GCAP-1), that regulate cGMP synthesis in photoreceptors. Cyclic GMP 207-211 guanylate cyclase 2D, retinal Homo sapiens 105-131 11387342-9 2001 We applied this method, referred to as COSUMAS (contact surfaces by mass spectrometry), to two proteins, retinal guanylyl cyclase 1 (RetGC1) and guanylyl cyclase-activating protein-1 (GCAP-1), that regulate cGMP synthesis in photoreceptors. Cyclic GMP 207-211 guanylate cyclase 2D, retinal Homo sapiens 133-139 10951519-9 2000 We postulate that the retGC1 mutations hinder the restoration of the basal level of cGMP of cone and rod photoreceptor cells, leading to a situation equivalent to consistent light exposure during photoreceptor development, explaining the severity of the visual disorder at birth. Cyclic GMP 84-88 guanylate cyclase 2D, retinal Homo sapiens 22-28 11306565-3 2001 In this study we show that cGMP synthesis by RetGC-1 requires dimerization, because critical functions in the catalytic site must be provided by each of the two polypeptide chains of the dimer. Cyclic GMP 27-31 guanylate cyclase 2D, retinal Homo sapiens 45-52 11136713-6 2001 Assays of cyclic guanosine monophosphate (cGMP) synthesis from guanosine triphosphate by RetGC1 in the presence of E6S/P50L showed that E6S/P50L could activate RetGC1 and displayed similar calcium sensitivity to wild-type GCAP1. Cyclic GMP 10-40 guanylate cyclase 2D, retinal Homo sapiens 89-95 11136713-6 2001 Assays of cyclic guanosine monophosphate (cGMP) synthesis from guanosine triphosphate by RetGC1 in the presence of E6S/P50L showed that E6S/P50L could activate RetGC1 and displayed similar calcium sensitivity to wild-type GCAP1. Cyclic GMP 42-46 guanylate cyclase 2D, retinal Homo sapiens 89-95 11136713-6 2001 Assays of cyclic guanosine monophosphate (cGMP) synthesis from guanosine triphosphate by RetGC1 in the presence of E6S/P50L showed that E6S/P50L could activate RetGC1 and displayed similar calcium sensitivity to wild-type GCAP1. Cyclic GMP 42-46 guanylate cyclase 2D, retinal Homo sapiens 160-166 10504230-1 1999 ROS-GC represents a membrane guanylate cyclase subfamily whose distinctive feature is that it transduces diverse intracellularly generated Ca(2+) signals into the production of the second messenger cyclic GMP. Cyclic GMP 198-208 guanylate cyclase 2D, retinal Homo sapiens 0-6 8944027-8 1996 Here, we report two missense mutations (F589S) and two frameshift mutations (nt 460 del C, nt 693 del C) of the retinal guanylate cyclase (RETGC, GDB symbol GUC2D) gene in four unrelated LCA1 probands of North African ancestry and ascribe LCA1 to an impaired production of cGMP in the retina, with permanent closure of cGMP-gated cation channels. Cyclic GMP 319-323 guanylate cyclase 2D, retinal Homo sapiens 112-137 10430891-9 1999 We suggest that the gain-of-function effects of R838C on RetGC-1 stimulated by GCAP-1, which are dominant in vitro and may cause an abnormal increase in cGMP synthesis in dark-adapted photoreceptors, may be the cause of the cone-rod degeneration. Cyclic GMP 153-157 guanylate cyclase 2D, retinal Homo sapiens 57-64 9305994-1 1997 In photoreceptor outer segments, particulate guanylyl cyclase (RetGC) is stimulated at low intracellular Ca2+ concentrations by guanylyl cyclase activating protein (GCAP), a Ca2+-sensitive activator, to resynthesize light-depleted cGMP. Cyclic GMP 231-235 guanylate cyclase 2D, retinal Homo sapiens 63-68 9544846-3 1998 Owing to the genetic heterogeneity of LCA and considering that LCA1 results from an impaired production of cGMP in the retina (with permanent closure of cGMP-gated cation channels), we hypothesized that the activation of the cGMP phosphodiesterase (PDE) could trigger the disease by lowering the intracellular cGMP level in the retina. Cyclic GMP 107-111 guanylate cyclase 2D, retinal Homo sapiens 63-67 9544846-3 1998 Owing to the genetic heterogeneity of LCA and considering that LCA1 results from an impaired production of cGMP in the retina (with permanent closure of cGMP-gated cation channels), we hypothesized that the activation of the cGMP phosphodiesterase (PDE) could trigger the disease by lowering the intracellular cGMP level in the retina. Cyclic GMP 153-157 guanylate cyclase 2D, retinal Homo sapiens 63-67 8944027-8 1996 Here, we report two missense mutations (F589S) and two frameshift mutations (nt 460 del C, nt 693 del C) of the retinal guanylate cyclase (RETGC, GDB symbol GUC2D) gene in four unrelated LCA1 probands of North African ancestry and ascribe LCA1 to an impaired production of cGMP in the retina, with permanent closure of cGMP-gated cation channels. Cyclic GMP 273-277 guanylate cyclase 2D, retinal Homo sapiens 112-137 8944027-8 1996 Here, we report two missense mutations (F589S) and two frameshift mutations (nt 460 del C, nt 693 del C) of the retinal guanylate cyclase (RETGC, GDB symbol GUC2D) gene in four unrelated LCA1 probands of North African ancestry and ascribe LCA1 to an impaired production of cGMP in the retina, with permanent closure of cGMP-gated cation channels. Cyclic GMP 273-277 guanylate cyclase 2D, retinal Homo sapiens 139-144 8944027-8 1996 Here, we report two missense mutations (F589S) and two frameshift mutations (nt 460 del C, nt 693 del C) of the retinal guanylate cyclase (RETGC, GDB symbol GUC2D) gene in four unrelated LCA1 probands of North African ancestry and ascribe LCA1 to an impaired production of cGMP in the retina, with permanent closure of cGMP-gated cation channels. Cyclic GMP 273-277 guanylate cyclase 2D, retinal Homo sapiens 157-162 8944027-8 1996 Here, we report two missense mutations (F589S) and two frameshift mutations (nt 460 del C, nt 693 del C) of the retinal guanylate cyclase (RETGC, GDB symbol GUC2D) gene in four unrelated LCA1 probands of North African ancestry and ascribe LCA1 to an impaired production of cGMP in the retina, with permanent closure of cGMP-gated cation channels. Cyclic GMP 319-323 guanylate cyclase 2D, retinal Homo sapiens 139-144 8944027-8 1996 Here, we report two missense mutations (F589S) and two frameshift mutations (nt 460 del C, nt 693 del C) of the retinal guanylate cyclase (RETGC, GDB symbol GUC2D) gene in four unrelated LCA1 probands of North African ancestry and ascribe LCA1 to an impaired production of cGMP in the retina, with permanent closure of cGMP-gated cation channels. Cyclic GMP 319-323 guanylate cyclase 2D, retinal Homo sapiens 157-162 1356371-4 1992 cGMP production by retGC is unaffected by any of the known natriuretic peptides. Cyclic GMP 0-4 guanylate cyclase 2D, retinal Homo sapiens 19-24 1356371-6 1992 Our results suggest that retGC may synthesize cGMP required for recovery of the dark state after phototransduction. Cyclic GMP 46-50 guanylate cyclase 2D, retinal Homo sapiens 25-30