tax-4 encodes the alpha (principal, pore-forming) subunit of a cyclic nucleotide-gated (CNG) cation channel, the C. elegans ortholog of vertebrate CNGA subunits. The channel is opened directly by intracellular cGMP (and, with lower sensitivity, cAMP) rather than by membrane voltage, and conducts Ca2+, Na+ and K+ across the membrane; a functionally important pore glutamate forms the selectivity filter and a C-linker gating ring couples cyclic-nucleotide binding in the cytoplasmic cyclic-nucleotide-binding domain to opening of the central gate. TAX-4 assembles as a homotetramer and can form a functional homomeric channel on its own, but in vivo it partners with the modulatory beta subunit TAX-2 (which cannot form a channel alone) to build the native sensory channel; the TAX-4/TAX-2 heteromer is markedly less cGMP-sensitive than the TAX-4 homomer. TAX-4 is expressed in many ciliated sensory neurons and is concentrated at their sensory endings, in the non-motile sensory cilium (including an inversin/NPHP-2-anchored proximal ciliary compartment in the AFD thermosensory neuron) and in dendrites. As the effector channel of cGMP-mediated signal transduction, TAX-4 is required for a broad range of sensory modalities, including thermosensation and thermotaxis, chemosensation and chemotaxis (including detection of CO2), oxygen sensing and aerotaxis, and light responses (phototransduction) in specific neurons; channel activity also feeds into downstream outputs such as sensory-neuron gene expression and the maintenance of sensory axon structure.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: TAX-4 is a plasma-membrane cyclic nucleotide-gated cation channel; gating cation flux across the plasma membrane at sensory endings is its site of action. Correct and core. |
| GO:0007606 sensory perception of chemical stimulus | IBA GO_REF:0000033 | ACCEPT | Summary: Chemosensation is a defining role of TAX-4: tax-4 mutants fail responses to water-soluble and volatile chemical attractants. Core process. Supporting Evidence: PMID:8893027 The C. elegans tax-4 mutants are abnormal in multiple sensory behaviors: they fail to respond to temperature or to water-soluble or volatile chemical attractants. |
| GO:0005222 intracellularly cAMP-activated cation channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: TAX-4 is a cyclic-nucleotide-gated channel that can also be activated by cAMP, though cGMP is the physiologically relevant ligand and the channel is cGMP-selective. Retained as a genuine (if secondary) channel activity. |
| GO:0005223 intracellularly cGMP-activated cation channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: This is the core molecular function of TAX-4: a directly cGMP-gated cation channel that is the effector of cGMP sensory signal transduction. |
| GO:0030553 cGMP binding | IBA GO_REF:0000033 | ACCEPT | Summary: TAX-4 has a cyclic-nucleotide-binding domain that binds cGMP to open the gate; cGMP binding is directly demonstrated by the cGMP-bound structures. Core. |
| GO:0098655 monoatomic cation transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: The channel conducts Ca2+, Na+ and K+ (non-selective cation permeation); monoatomic cation transmembrane transport is the accurate transport-process term. Core. |
| GO:0017071 intracellular cyclic nucleotide activated cation channel complex | IBA GO_REF:0000033 | ACCEPT | Summary: TAX-4 is a subunit of the cyclic-nucleotide-gated cation channel complex (homotetramer in vitro; native TAX-4/TAX-2 heteromer). Correct complex term. |
| GO:0005216 monoatomic ion channel activity | IEA GO_REF:0000002 | ACCEPT | Summary: Accurate but generic parent of the specific cGMP-gated cation channel activity. Retained; the informative term is GO:0005223. |
| GO:0005221 intracellularly cyclic nucleotide-activated monoatomic cation channel activity | IEA GO_REF:0000002 | ACCEPT | Summary: Accurate family-level CNG channel molecular-function term; a direct parent of the cGMP- and cAMP-activated specific terms already annotated. |
| GO:0005249 voltage-gated potassium channel activity | IEA GO_REF:0000002 | REMOVE | Summary: Incorrect. TAX-4 is a non-selective cation CNG channel, NOT a voltage-gated, K+-selective channel. The cryo-EM structure shows an unusual voltage-sensor-like domain accounting for its deficient voltage dependence. This IEA term is an over-propagation from the shared EAG/ELK/ERG-family InterPro signature and should be removed. Supporting Evidence: PMID:28099415 The channel has an unusual voltage-sensor-like domain, accounting for its deficient voltage dependence. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Plasma-membrane localization (UniProt subcellular-location mapping), consistent with the cryo-EM cell-membrane assignment and ciliary/dendritic membrane localization. Correct and core. |
| GO:0005929 cilium | IEA GO_REF:0000044 | ACCEPT | Summary: TAX-4 localizes to sensory cilia; a more specific experimental term (non-motile cilium, GO:0097730) is also annotated. Correct. |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000002 | ACCEPT | Summary: Accurate but generic parent of monoatomic cation transmembrane transport. Retained. |
| GO:0006813 potassium ion transport | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Over-annotation. TAX-4 is a non-selective cation channel that does conduct K+, but it is not a dedicated potassium transporter; the K+-specific process term comes from the K-channel-family InterPro signature. The accurate term is monoatomic cation transmembrane transport (GO:0098655). |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Generic membrane location; true but superseded by plasma membrane / cilium. Retained. |
| GO:0034703 cation channel complex | IEA GO_REF:0000117 | ACCEPT | Summary: TAX-4 is part of a cation channel complex (the CNG channel). Correct; also supported experimentally (PMID:10064800). |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: Accurate but generic parent process. Retained. |
| GO:0070482 response to oxygen levels | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The tax-2/tax-4 CNG channel is required for O2-evoked responses and hyperoxia avoidance; also supported experimentally. A downstream sensory output rather than the core channel function. |
| GO:0071805 potassium ion transmembrane transport | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Over-annotation, same rationale as GO:0006813: non-selective cation channel wrongly cast as a K+-specific transporter via the K-channel InterPro signature. Use monoatomic cation transmembrane transport (GO:0098655). |
| GO:0042802 identical protein binding | IPI PMID:28099415 Structure of a eukaryotic cyclic-nucleotide-gated channel. | KEEP AS NON CORE | Summary: Reflects TAX-4 self-association into a homotetramer, directly seen in the cryo-EM structure (PMID:28099415), which solved the channel as a homotetramer. Accurate but low-information on its own; the tetramer is captured better by the channel-complex terms (GO:0017071, GO:0034703). Kept as reported. |
| GO:0042802 identical protein binding | IPI PMID:32483338 Mechanism of ligand activation of a eukaryotic cyclic nucleo... | KEEP AS NON CORE | Summary: Duplicate self-association (homotetramer) evidence from the second cryo-EM structure. Kept as reported; non-core. |
| GO:0097730 non-motile cilium | IDA PMID:31259686 The Caenorhabditis elegans Tubby homolog dynamically modulat... | ACCEPT | Summary: TAX-4 is a ciliary CNG channel; UniProt records ciliary subcellular location from this study. Core cellular component. |
| GO:0034703 cation channel complex | IDA PMID:10064800 Functional reconstitution of a heteromeric cyclic nucleotide... | ACCEPT | Summary: Functional reconstitution shows TAX-4 and TAX-2 form a heteromeric cation channel in cultured cells. Directly supports channel-complex membership. Core. Supporting Evidence: PMID:10064800 Here we show that TAX-4 and TAX-2 form a heteromeric channel when expressed in HEK293 cells, but TAX-2 does not form a channel on its own. |
| GO:0003031 detection of carbon dioxide | IMP PMID:24240097 A chemoreceptor that detects molecular carbon dioxide. | KEEP AS NON CORE | Summary: CO2 detection in BAG (and other) neurons requires the tax-2/tax-4 cGMP-gated channel downstream of the receptor guanylyl cyclase GCY-9. A specific chemosensory modality; retained as a downstream consequence of the core channel function. (Cited paper is abstract-only in the cache; the tax-4 requirement for CO2 responses is independently established in PMID:21435556.) |
| GO:0019722 calcium-mediated signaling | IMP PMID:24240097 A chemoreceptor that detects molecular carbon dioxide. | KEEP AS NON CORE | Summary: Channel opening admits Ca2+, driving the calcium signal in chemosensory neurons. A downstream signaling consequence of cation channel activity; non-core. |
| GO:0010628 positive regulation of gene expression | IMP PMID:25303524 Chemosensation of bacterial secondary metabolites modulates ... | KEEP AS NON CORE | Summary: In ASJ, TAX-4-dependent chemosensory signaling induces expression of the DAF-7/TGF-beta neuromodulator on exposure to P. aeruginosa metabolites. An indirect, activity-dependent transcriptional output; non-core. Supporting Evidence: PMID:25303524 secondary metabolites produced by Pseudomonas aeruginosa modulates a neuroendocrine signaling pathway that promotes avoidance behavior |
| GO:0050907 detection of chemical stimulus involved in sensory perception | IMP PMID:24240097 A chemoreceptor that detects molecular carbon dioxide. | ACCEPT | Summary: TAX-4 is the effector channel for detection of chemical stimuli in sensory neurons; an accurate general term for its core sensory role. Core. |
| GO:0007602 phototransduction | IMP PMID:20436480 C. elegans phototransduction requires a G protein-dependent ... | KEEP AS NON CORE | Summary: In the ASJ photoreceptor neuron, light-evoked cGMP opens cGMP-sensitive CNG channels; TAX-4 is required for this response. A specialized downstream sensory modality; non-core. Supporting Evidence: PMID:20436480 opening of cGMP-sensitive CNG channels and stimulation of photoreceptor cells. |
| GO:0007199 G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger | IMP PMID:20436480 C. elegans phototransduction requires a G protein-dependent ... | KEEP AS NON CORE | Summary: TAX-4 acts as the cGMP-gated effector at the end of a G-protein/cGMP phototransduction cascade in ASJ. Retained as a downstream pathway role; non-core. Supporting Evidence: PMID:20436480 phototransduction in ASJ is a G protein-mediated process and requires membrane-associated guanylate cyclases |
| GO:0040040 thermosensory behavior | IMP PMID:21315599 Regulation of response properties and operating range of the... | ACCEPT | Summary: Mutations in the tax-4 CNG channel abolish AFD thermosensitivity and isothermal tracking (per this study's electrophysiology and behavior). Thermosensation is a flagship sensory role of TAX-4. Core. Supporting Evidence: PMID:21315599 These results indicate that the AFD neurons and TAX-4 CNG channel are required to both initiate and maintain isothermal tracks. |
| GO:0043052 thermotaxis | IMP PMID:21315599 Regulation of response properties and operating range of the... | KEEP AS NON CORE | Summary: Thermotaxis (isothermal tracking) is the behavioral output of AFD thermosensation that requires TAX-4. A downstream behavior; non-core. |
| GO:0010754 negative regulation of receptor guanylyl cyclase signaling pathway | IMP PMID:23940325 In vivo genetic dissection of O2-evoked cGMP dynamics in a C... | KEEP AS NON CORE | Summary: In O2-sensing neurons, cGMP-gated channel activity (Ca2+ entry) drives Ca2+-dependent negative-feedback loops that shape cGMP dynamics. A feedback role secondary to the core channel function; non-core. Supporting Evidence: PMID:23940325 Increased cGMP leads to a sustained Ca(2+) response in the neuron that depends on cGMP-gated ion channels. |
| GO:0070482 response to oxygen levels | IMP PMID:23940325 In vivo genetic dissection of O2-evoked cGMP dynamics in a C... | KEEP AS NON CORE | Summary: TAX-4-containing cGMP-gated channels transduce O2-evoked cGMP into sustained Ca2+ responses in the gas-sensing neuron. Downstream sensory output; non-core. |
| GO:0040010 positive regulation of growth rate | IGI PMID:15530424 A new putative cyclic nucleotide-gated channel gene, cng-3, ... | KEEP AS NON CORE | Summary: Genetic-interaction annotation from a study primarily on the cng-3 CNG channel and thermotolerance, with tax-4 as background. A pleiotropic physiological consequence; non-core. (Cited paper abstract-only in cache.) |
| GO:0097543 ciliary inversin compartment | IDA PMID:25335890 Ciliopathy proteins establish a bipartite signaling compartm... | ACCEPT | Summary: In AFD, NPHP-2/inversin anchors the cGMP-gated ion channel within the proximal ciliary (inversin) compartment. Directly supports this specific ciliary sub-compartment localization. Core cellular component. Supporting Evidence: PMID:25335890 requires NPHP-2 (known as inversin in mammals) to anchor a cGMP-gated ion channel within the proximal ciliary region. |
| GO:0097730 non-motile cilium | IDA PMID:25335890 Ciliopathy proteins establish a bipartite signaling compartm... | ACCEPT | Summary: TAX-4/TAX-2 cGMP-gated channel localizes to the AFD sensory cilium. Core cellular component. |
| GO:0005223 intracellularly cGMP-activated cation channel activity | IDA PMID:10064800 Functional reconstitution of a heteromeric cyclic nucleotide... | ACCEPT | Summary: Direct functional reconstitution in cultured cells demonstrates a cGMP-gated cation channel. Core molecular function. Supporting Evidence: PMID:10064800 The heteromeric TAX-4/TAX-2 channel is 25-fold less sensitive to cGMP than the TAX-4 channel, but it remains highly selective for cGMP over cAMP. |
| GO:0098655 monoatomic cation transmembrane transport | IDA PMID:10064800 Functional reconstitution of a heteromeric cyclic nucleotide... | ACCEPT | Summary: Reconstituted channel conducts cations across the membrane. Core transport process. |
| GO:0097730 non-motile cilium | IDA PMID:23886944 Cell- and subunit-specific mechanisms of CNG channel ciliary... | ACCEPT | Summary: Study defines sequences and trans-acting factors required for ciliary targeting/localization of the TAX-4 CNGA and TAX-2 CNGB subunits. Directly supports ciliary localization. Core cellular component. Supporting Evidence: PMID:23886944 sequences required for efficient ciliary targeting and localization of the TAX-2 CNGB and TAX-4 CNGA subunits. |
| GO:0006935 chemotaxis | IMP PMID:21435556 Temperature, oxygen, and salt-sensing neurons in C. elegans ... | KEEP AS NON CORE | Summary: CO2-evoked responses and CO2 avoidance behavior require cGMP-gated channels containing TAX-2 and TAX-4. Chemotaxis is a behavioral output of the core chemosensory channel function; retained as non-core for this study. Supporting Evidence: PMID:21435556 CO(2)-evoked Ca(2+) responses in AFD and BAG neurons require cGMP-gated ion channels. |
| GO:0070482 response to oxygen levels | IMP PMID:19323996 Neurons detect increases and decreases in oxygen levels usin... | KEEP AS NON CORE | Summary: URX and BAG O2-sensing neurons use cGMP signaling (via sGCs) that is transduced by CNG channels; tax-4 is required for O2 responses. Downstream sensory output; non-core. |
| GO:0005222 intracellularly cAMP-activated cation channel activity | IDA PMID:8893027 Mutations in a cyclic nucleotide-gated channel lead to abnor... | ACCEPT | Summary: TAX-4 expressed in cultured cells functions as a cyclic-nucleotide-gated channel (cAMP-responsive as well as cGMP-gated). Genuine channel activity, though cGMP is physiologically dominant. Supporting Evidence: PMID:8893027 Tax-4 protein expressed in cultured cells functions as a cyclic nucleotide-gated channel. |
| GO:0005223 intracellularly cGMP-activated cation channel activity | IDA PMID:8893027 Mutations in a cyclic nucleotide-gated channel lead to abnor... | ACCEPT | Summary: Original demonstration that TAX-4 forms a cyclic-nucleotide-gated channel; cGMP is the key intracellular messenger in worm sensory transduction. Core molecular function. Supporting Evidence: PMID:8893027 The results suggest that a cyclic nucleotide-gated channel is required for thermosensation and chemosensation |
| GO:0030425 dendrite | IDA PMID:8893027 Mutations in a cyclic nucleotide-gated channel lead to abnor... | ACCEPT | Summary: TAX-4::GFP localizes at the sensory endings of thermosensory, gustatory and olfactory neurons (dendritic sensory endings/cilia). Core cellular component. Supporting Evidence: PMID:8893027 The Tax-4::GFP fusion is partly localized at the sensory endings of these neurons. |
| GO:0097730 non-motile cilium | IDA PMID:8893027 Mutations in a cyclic nucleotide-gated channel lead to abnor... | ACCEPT | Summary: TAX-4 localizes to the sensory endings (cilia) of ciliated sensory neurons. Core cellular component. Supporting Evidence: PMID:8893027 expressed in thermosensory, gustatory, and olfactory neurons mediating all the sensory behaviors affected by the tax-4 mutations |
| GO:0030516 regulation of axon extension | IMP PMID:9486798 A cyclic nucleotide-gated channel inhibits sensory axon outg... | KEEP AS NON CORE | Summary: tax-2/tax-4 are required to maintain correct sensory axon structure; mutants show inappropriate late-larval axon outgrowth. A pleiotropic developmental/maintenance role distinct from acute sensory transduction; non-core. Supporting Evidence: PMID:9486798 tax-2 and tax-4 are required for the maintenance of correct axon structure |
| GO:0009454 aerotaxis | IMP PMID:15220933 Oxygen sensation and social feeding mediated by a C. elegans... | KEEP AS NON CORE | Summary: Avoidance of high oxygen requires the sensory cGMP-gated channel tax-2/tax-4 plus the sGC gcy-35. Aerotaxis is a downstream O2-driven behavior; non-core. Supporting Evidence: PMID:15220933 Avoidance of high oxygen levels by C. elegans requires the sensory cGMP-gated channel tax-2/tax-4 and a specific soluble guanylate cyclase homologue, gcy-35. |
| GO:0055093 response to hyperoxia | IMP PMID:15220933 Oxygen sensation and social feeding mediated by a C. elegans... | KEEP AS NON CORE | Summary: TAX-4-dependent O2 sensation mediates avoidance of hyperoxic environments. Downstream sensory output; non-core. |
| GO:0040040 thermosensory behavior | IMP PMID:11879652 Negative regulation and gain control of sensory neurons by t... | ACCEPT | Summary: Thermosensory behavior requiring TAX-4, assayed here in the context of the TAX-6 calcineurin gain-control pathway. Thermosensation is a core TAX-4 sensory role. |
| GO:0040040 thermosensory behavior | IGI PMID:11879652 Negative regulation and gain control of sensory neurons by t... | ACCEPT | Summary: Genetic-interaction (with tax-6) evidence corroborating TAX-4's core thermosensory-behavior role. |
| GO:0042048 olfactory behavior | IMP PMID:11879652 Negative regulation and gain control of sensory neurons by t... | KEEP AS NON CORE | Summary: Olfaction is one of the sensory modalities requiring TAX-4; here in the context of tax-6-mediated adaptation/gain control. A downstream behavioral output; non-core. |
| GO:0042048 olfactory behavior | IGI PMID:11879652 Negative regulation and gain control of sensory neurons by t... | KEEP AS NON CORE | Summary: Genetic-interaction evidence for an olfactory-behavior role. Non-core. |
| GO:0043052 thermotaxis | IMP PMID:11879652 Negative regulation and gain control of sensory neurons by t... | KEEP AS NON CORE | Summary: Thermotaxis behavior involving TAX-4 in the tax-6 gain-control study. Downstream behavior; non-core. |
| GO:0043052 thermotaxis | IGI PMID:11879652 Negative regulation and gain control of sensory neurons by t... | KEEP AS NON CORE | Summary: Genetic-interaction evidence for a thermotaxis role. Non-core. |
| GO:0040040 thermosensory behavior | IMP PMID:14711416 The CMK-1 CaMKI and the TAX-4 Cyclic nucleotide-gated channe... | ACCEPT | Summary: CMK-1 and TAX-4 regulate AFD thermosensory-neuron gene expression, morphology and function. Thermosensation is a core TAX-4 role; well supported. Supporting Evidence: PMID:14711416 the CMK-1 Ca2+/calmodulin-dependent protein kinase I (CaMKI) and the TAX-4 cyclic nucleotide-gated channel regulate gene expression, morphology, and functions of the AFD thermosensory neurons. |
| GO:0045664 regulation of neuron differentiation | IMP PMID:14711416 The CMK-1 CaMKI and the TAX-4 Cyclic nucleotide-gated channe... | KEEP AS NON CORE | Summary: TAX-4 activity is required to maintain AFD-specific gene expression and morphology; an activity-dependent effect on neuronal differentiation state rather than a direct role. Non-core. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:14711416 The CMK-1 CaMKI and the TAX-4 Cyclic nucleotide-gated channe... | KEEP AS NON CORE | Summary: TAX-4 channel activity is required to maintain AFD-specific gene expression. This is an indirect, activity-dependent transcriptional consequence; TAX-4 is a channel, not a transcriptional regulator. Non-core. Supporting Evidence: PMID:14711416 TAX-4 functions are required during larval stages to maintain gene expression in the adult. |
| GO:0048812 neuron projection morphogenesis | IMP PMID:14711416 The CMK-1 CaMKI and the TAX-4 Cyclic nucleotide-gated channe... | KEEP AS NON CORE | Summary: TAX-4 activity influences AFD sensory-ending morphology. A downstream, activity-dependent morphological effect; non-core. |
| GO:0007635 chemosensory behavior | IMP PMID:8893027 Mutations in a cyclic nucleotide-gated channel lead to abnor... | ACCEPT | Summary: tax-4 mutants are defective in chemosensory behaviors (gustation and olfaction). Core sensory role. Supporting Evidence: PMID:8893027 The C. elegans tax-4 mutants are abnormal in multiple sensory behaviors: they fail to respond to temperature or to water-soluble or volatile chemical attractants. |
| GO:0016020 membrane | NAS PMID:8893027 Mutations in a cyclic nucleotide-gated channel lead to abnor... | ACCEPT | Summary: Generic membrane localization (NAS). True but superseded by plasma membrane / cilium / dendrite. Retained. |
| GO:0030553 cGMP binding | NAS PMID:8893027 Mutations in a cyclic nucleotide-gated channel lead to abnor... | ACCEPT | Summary: cGMP binding inferred (NAS) from the CNG-channel homology and cGMP-gated activity; later confirmed structurally. Core molecular function. |
| GO:0040040 thermosensory behavior | IMP PMID:8893027 Mutations in a cyclic nucleotide-gated channel lead to abnor... | ACCEPT | Summary: Original genetic evidence that tax-4 is required for thermosensation (mutants fail to respond to temperature). Core sensory role. Supporting Evidence: PMID:8893027 they fail to respond to temperature or to water-soluble or volatile chemical attractants. |
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Download this section (compressed HTML)Q: What is the endogenous TAX-4:TAX-2 subunit stoichiometry of the native sensory channel, and does it differ between neuron types or between ciliary subcompartments within a single neuron?
Q: Which neurons rely on the highly cGMP-sensitive TAX-4 homomer versus the less-sensitive TAX-4/TAX-2 heteromer, and how does that choice set each cell's stimulus threshold and dynamic range?
Experiment: Quantitative in vivo measurement of TAX-4 and TAX-2 subunit copy number / ratio in defined sensory cilia (e.g. calibrated fluorescence or single-molecule counting) combined with cell-specific cGMP dose-response electrophysiology in tax-2(+) versus tax-2(-) backgrounds, to map homomeric versus heteromeric channels onto neurons and quantify how TAX-2 tunes cGMP sensitivity in situ.
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