GUCA1A encodes GCAP1, an EF-hand calcium sensor in retinal photoreceptors. It regulates membrane guanylate cyclases to restore cGMP during photoresponse recovery. Pathogenic variants can impair calcium-dependent cyclase control and cause cone or cone-rod dystrophy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001750 photoreceptor outer segment | IEA GO_REF:0000120 | ACCEPT | Summary: Retain outer-segment localization across rods and cones. Reason: Human GCAP1 is detected in both rod and cone outer segments; retaining this broader location preserves the observed rod distribution. Supporting Evidence: file:human/GUCA1A/GUCA1A-source-evidence.json file:human/GUCA1A/GUCA1A-uniprot.txt Present at higher levels in cone than in rod outer segments |
| GO:0001917 photoreceptor inner segment | IBA GO_REF:0000033 | ACCEPT | Reason: AN434 supports the inherited is_active_in assertion. Target localization provides legitimate self-donor grounding; the activity qualifier remains a phylogenetic interpretation. Supporting Evidence: GO_REF:0000033 file:human/GUCA1A/GUCA1A-source-evidence.json |
| GO:0001917 photoreceptor inner segment | IDA PMID:9620085 The localization of guanylyl cyclase-activating proteins in ... | ACCEPT | Reason: The original human retinal sections show GCAP1 in photoreceptor inner segments; this is protein immunostaining. Supporting Evidence: |
| GO:0001917 photoreceptor inner segment | IEA GO_REF:0000120 | ACCEPT | Reason: Human and rodent retinal immunostaining supports inner-segment localization; this retains location without asserting compartment-specific activity. |
| GO:0005509 calcium ion binding | IBA GO_REF:0000033 | ACCEPT | Reason: The exact human sequence descends from AN2/PTN000550679, with conserved predicted calcium-binding sites and experimentally grounded descendant annotations. Supporting Evidence: GO_REF:0000033 file:human/GUCA1A/GUCA1A-source-evidence.json |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Reason: The retained EF-hand domains and functional calcium binding support this calcium-sensor activity. |
| GO:0005509 calcium ion binding | ISS GO_REF:0000024 | ACCEPT | Reason: Wild-type bovine GCAP1 calcium-binding measurements support the ortholog transfer; mutant-specific structural properties are not transferred. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Reason: GSC2 association is experimentally supported; its predicted nuclear homeobox context supplies no evidence that GCAP1 regulates transcription. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Reason: The AGR2 assay association is supported. Secretion is experimental and ER placement by similarity; endogenous encounter with intracellular GCAP1 remains unestablished. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Reason: PRKAR1B binds in the assay and has experimental membrane targeting; this establishes neither endogenous colocalization nor GCAP1 regulation of PKA. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Reason: DDIT4L association is supported; cytoplasmic placement is inferred and TOR regulation established, without evidence assigning GCAP1 a TOR-regulatory role. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Reason: DEFB118 association is supported in yeast. Its secreted epididymal context leaves native photoreceptor encounter unestablished, without falsifying assay binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Reason: KATNAL1 association is supported; its experimental cytoplasmic/spindle localization and microtubule severing do not establish a corresponding GCAP1 activity. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Reason: C1QTNF5 association is supported; secreted RPE/ciliary-body localization does not establish photoreceptor colocalization or shared membrane sidedness with GCAP1. |
| GO:0007165 signal transduction | NAS PMID:7983048 Molecular characterization of human and mouse photoreceptor ... | ACCEPT | Reason: GCAP1 directly regulates cyclase in photoreceptor calcium signaling. |
| GO:0007601 visual perception | IBA GO_REF:0000033 | ACCEPT | Reason: AN434 places the visual perception assertion on the verified GCAP1 lineage. Experimental target annotations provide legitimate descendant grounding despite differing donor snapshots. Supporting Evidence: GO_REF:0000033 file:human/GUCA1A/GUCA1A-source-evidence.json |
| GO:0007601 visual perception | IMP PMID:18706439 A novel GCAP1(N104K) mutation in EF-hand 3 (EF3) linked to a... | ACCEPT | Reason: Human N104K carriers show progressive cone dysfunction and delayed paired-flash rod recovery. These clinical observations support GCAP1 participation in vision. Supporting Evidence: |
| GO:0007601 visual perception | IMP PMID:30184081 A novel p.(Glu111Val) missense mutation in GUCA1A associated... | ACCEPT | Reason: The human E111V family has cone-rod dysfunction, with impaired calcium-dependent cyclase regulation established by recombinant human-protein assays. Supporting Evidence: |
| GO:0007601 visual perception | TAS PMID:9425234 A mutation in guanylate cyclase activator 1A (GUCA1A) in an ... | ACCEPT | Reason: Y99C segregation in a human cone-dystrophy pedigree supports the established visual role; the proposed molecular mechanism is not an assay result. Supporting Evidence: |
| GO:0008048 calcium sensitive guanylate cyclase activator activity | IBA GO_REF:0000033 | ACCEPT | Reason: AN434/PTN002746597 contains human GCAP1 and experimentally grounded activator donors. The retained target lineage has no recorded loss of this inference. Supporting Evidence: GO_REF:0000033 file:human/GUCA1A/GUCA1A-source-evidence.json |
| GO:0008048 calcium sensitive guanylate cyclase activator activity | IEA GO_REF:0000107 | ACCEPT | Reason: Mouse knockout and recombinant GCAP1 add-back establish calcium-sensitive cyclase regulation, supporting the activator transfer. |
| GO:0008048 calcium sensitive guanylate cyclase activator activity | ISS GO_REF:0000024 | ACCEPT | Reason: Wild-type bovine GCAP1 activates human RetGC1 in vitro under calcium control, supporting this regulatory activity. |
| GO:0008048 calcium sensitive guanylate cyclase activator activity | TAS PMID:9425234 A mutation in guanylate cyclase activator 1A (GUCA1A) in an ... | ACCEPT | Reason: Calcium-sensitive activation is established; later reconstitution tests human proteins beyond the original pedigree evidence. |
| GO:0009966 regulation of signal transduction | IBA GO_REF:0000033 | ACCEPT | Reason: The target inherits AN1/PTN008588905, supported by experimental signaling regulation annotations in descendants. Cyclase regulation has no verified ontology refinement path to this term. Supporting Evidence: GO_REF:0000033 file:human/GUCA1A/GUCA1A-source-evidence.json |
| GO:0016020 membrane | IEA GO_REF:0000044 | TOO GENERAL | Reason: Accepted located_in disc membrane annotations provide an is_a refinement; the separate is_active_in assertion is not the comparator. Supporting Evidence: file:human/GUCA1A/GUCA1A-source-evidence.json |
| GO:0030249 guanylate cyclase regulator activity | IEA GO_REF:0000107 | ACCEPT | Reason: Regulation includes activation and suppression; the activator child alone omits the latter. |
| GO:0030249 guanylate cyclase regulator activity | IMP PMID:30622141 A G86R mutation in the calcium-sensor protein GCAP1 alters r... | ACCEPT | Reason: Human GCAP1 regulates human RetGC1 across calcium concentrations, including activation and calcium-dependent deceleration. GCAP1–3/NHERF4 comparisons leave inhibitor annotation unresolved. |
| GO:0030249 guanylate cyclase regulator activity | ISS GO_REF:0000024 | ACCEPT | Reason: Regulation includes activation and suppression; the activator child alone omits the latter. |
| GO:0030250 guanylate cyclase activator activity | IMP PMID:30622141 A G86R mutation in the calcium-sensor protein GCAP1 alters r... | TOO GENERAL | Reason: The retained calcium-sensitive guanylate cyclase activator activity is an is_a descendant that specifies this activation function. |
| GO:0031284 positive regulation of guanylate cyclase activity | ISS GO_REF:0000024 | ACCEPT | Reason: The donor directly increases RetGC1 activity; GCAP1 regulates the cyclase rather than catalysing GTP conversion. |
| GO:0036368 photoresponse recovery | IMP PMID:19459154 Mutations in the GUCA1A gene involved in hereditary cone dys... | ACCEPT | Reason: Human variants and bovine reconstitution support disturbed calcium-dependent cyclase control. Retain recovery participation, corroborated by independent human paired-flash measurements. |
| GO:0036368 photoresponse recovery | IMP PMID:30184081 A novel p.(Glu111Val) missense mutation in GUCA1A associated... | ACCEPT | Reason: Human E111V genetics and biochemical reconstitution support disrupted recovery feedback. Retain the curated process and its visual-perception extension; the clinical ERGs were not paired-flash recovery measurements. Supporting Evidence: |
| GO:0042622 photoreceptor outer segment membrane | IDA PMID:9620085 The localization of guanylyl cyclase-activating proteins in ... | MARK AS OVER ANNOTATED | Reason: Human immunostaining supports outer segments, but surrounding-membrane activity exceeds its spatial resolution. UniProt's experimental location assignment is acknowledged; the cone-cell context is retained. |
| GO:0071277 cellular response to calcium ion | ISS GO_REF:0000024 | ACCEPT | Reason: Calcium-dependent conformational switching provides a direct molecular response, supporting this sensor-associated cellular process. |
| GO:0097381 photoreceptor disc membrane | IEA GO_REF:0000117 | ACCEPT | Reason: The electronic disc-membrane location agrees with an explicit human P43080 leaf in the independently inspected Reactome event. Supporting Evidence: Reactome:R-HSA-2586748 file:human/GUCA1A/GUCA1A-source-evidence.json |
| GO:0097381 photoreceptor disc membrane | TAS Reactome:R-HSA-2586748 | ACCEPT | Reason: Both event paths reach human P43080 residues 2–201 explicitly assigned to disc membrane, retaining this curated protein location. Supporting Evidence: Reactome:R-HSA-2586748 file:human/GUCA1A/GUCA1A-source-evidence.json |
| GO:0120199 cone photoreceptor outer segment | IBA GO_REF:0000033 | ACCEPT | Reason: The verified AN434 cone outer segment assertion includes experimental target grounding. The self-donor is legitimate, and the activity location qualifier is preserved. Supporting Evidence: GO_REF:0000033 file:human/GUCA1A/GUCA1A-source-evidence.json |
| GO:0120199 cone photoreceptor outer segment | IDA PMID:9620085 The localization of guanylyl cyclase-activating proteins in ... | ACCEPT | Reason: Human cone outer segments stain strongly for GCAP1 in the original study. Retain the observed compartment. Supporting Evidence: |
| GO:0120199 cone photoreceptor outer segment | IEA GO_REF:0000107 | ACCEPT | Reason: The mouse donor localization agrees with directly inspected human cone outer-segment immunostaining, supporting this unextended location. |
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