CACNA1D encodes the pore-forming alpha1D subunit of CaV1.3, an L-type voltage-gated calcium channel. Calcium entry through the channel couples membrane depolarization to electrical and secretory responses. Its relatively negative activation range within the L-type family supports sinoatrial pacemaking and calcium-dependent neurotransmitter release from cochlear inner hair cells, with additional functions in neurons and endocrine cells. Beta and alpha2delta subunits regulate channel expression and gating, and intracellular partners organize local signaling. C-terminal alternative splicing changes activation and calcium-dependent inactivation. Loss-of-function variants can impair hearing and sinoatrial-node function, whereas activating variants can perturb adrenal and neuronal calcium signaling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005216 monoatomic ion channel activity | IEA GO_REF:0000002 | MODIFY | Summary: The broad channel-domain inference can be refined to established L-type calcium-channel activity. Reason: Human alpha1D expression and voltage-clamp recordings identify the calcium-selective, voltage-gated channel. The official GO:0008331 scope includes L-type channels. CaV1.3 activation at relatively negative potentials within this family does not make it a T-type channel. This refinement uses a term already in the source set. Proposed replacements: high voltage-gated calcium channel activity |
| GO:0005245 voltage-gated calcium channel activity | IDA PMID:11160515 Biophysical properties, pharmacology, and modulation of huma... | ACCEPT | Summary: Human neuronal alpha1D supports voltage-gated calcium currents. Reason: The complete abstract describes human alpha1D with alpha2delta1 and beta3a in HEK293 cells, including calcium- and barium-current measurements, voltage dependence and dihydropyridine pharmacology. Failure of several Gi/o-linked pathways to modulate this preparation is a condition-specific regulatory result, not failure of channel function. Supporting Evidence: PMID:11160515 The currents were high-voltage activated |
| GO:0005245 voltage-gated calcium channel activity | IDA PMID:21131953 Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy... | ACCEPT | Summary: WT and nonconducting human SANDD channels establish the calcium-channel function. Reason: The complete PMID:21131953 abstract identifies the pore-forming alpha1D subunit and a glycine insertion that yields nonconducting channels with abnormal voltage-dependent gating. The normal function is established through the expressed channel comparison; the pathogenic mutant is not treated as the normal protein. Full Methods and figures were unavailable in the canonical cache. Supporting Evidence: PMID:21131953 resulted in nonconducting calcium channels |
| GO:0005245 voltage-gated calcium channel activity | IEA GO_REF:0000002 | ACCEPT | Summary: The conserved channel-domain annotation agrees with direct human channel assays. Reason: The InterPro inference is independently corroborated by human alpha1D functional expression. Original domain sources are preserved without claiming that their mapping implementation was re-created. |
| GO:0005245 voltage-gated calcium channel activity | IMP PMID:23913001 Somatic and germline CACNA1D calcium channel mutations in al... | ACCEPT | Summary: Human WT and adrenal-disease-associated mutant channels directly support channel activity. Reason: Selected complete primary Results and Methods describe human CACNA1D WT and pore-region variants coexpressed with beta2a and alpha2delta1 in HEK293T cells. Mutations shift activation and alter inactivation; current-density effects differ among variants. Increased calcium influx in adrenal disease is mechanistically interpreted from these assays, not an aldosterone-synthetic activity of alpha1D. Supporting Evidence: PMID:23913001 channel activation at less depolarized potentials |
| GO:0005262 calcium channel activity | IMP PMID:25620733 CACNA1D de novo mutations in autism spectrum disorders activ... | ACCEPT | Summary: The human channel conducts calcium and is altered by A749G and G407R. Reason: The complete abstract and selected Methods/Results describe human long-C-terminal alpha1D in tsA-201 cells with calcium as charge carrier. A749G shifts gating and increases peak current, whereas G407R can reduce peak amplitude while greatly prolonging current. The two effects support calcium-channel activity without collapsing all gain-of-function mechanisms into increased peak current. Supporting Evidence: PMID:25620733 pronounced slowing of current inactivation during depolarizing stimuli |
| GO:0005262 calcium channel activity | IMP PMID:28472301 New gain-of-function mutation shows CACNA1D as recurrently m... | ACCEPT | Summary: WT and V401L splice-variant recordings substantiate calcium-channel activity. Reason: The inspected Methods/Results compare human long and short 43s channel constructs in tsA-201 cells. V401L increases calcium entry through gating and inactivation changes that depend on splice context. The short 43s construct is not automatically equated with the separately named 42A product. Clinical risk interpretation is kept separate from the measured channel activity. Supporting Evidence: PMID:28472301 shifted voltage dependence of activation and inactivation to more negative voltages |
| GO:0005515 protein binding | IPI PMID:30058071 Solution structures of the SH3 domains from Shank scaffold p... | MODIFY | Summary: Cav1.3 binds Shank SH3 domains through a channel-derived region; the curated source specifies SHANK3-1. Reason: PMID:30058071 directly describes binding between Shank SH3 domains and a Cav1.3 region containing a cluster of arginine residues. This supports SH3 domain binding rather than only generic protein binding. The exact human CACNA1D–SHANK3-1 edge is also retained in the UniProt IntAct list. The complete abstract and publisher supplementary-information descriptions were read, but the full main text and underlying figures were not accessible/read. Preserve Q9BYB0-1 as the curated partner; do not infer that this interaction is unique to that isoform or that the isolated-domain experiment establishes a native full-channel scaffold complex. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:30058071 the SH3 domains binds to a Cav1.3 region file:human/CACNA1D/CACNA1D-uniprot.txt |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of GRID2IP is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–GRID2IP (A4D2P6) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 PDZ domains and their target PDZ-binding motifs file:human/CACNA1D/CACNA1D-uniprot.txt |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of MPDZ is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–MPDZ (O75970) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of DLG4 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–DLG4 (P78352) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of APBA1 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–APBA1 (Q02410) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of TJP1 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–TJP1 (Q07157) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of DLG1 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–DLG1 (Q12959) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of IL16 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–IL16 (Q14005) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of SCRIB is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–SCRIB (Q14160) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of PDZK1 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–PDZK1 (Q5T2W1) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of FRMPD2 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–FRMPD2 (Q68DX3) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of MAGI2 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–MAGI2 (Q86UL8) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of LNX2 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–LNX2 (Q8N448) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of PATJ is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–PATJ (Q8NI35) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of LNX1 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–LNX1 (Q8TBB1) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of DLG3 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–DLG3 (Q92796) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of APBA2 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–APBA2 (Q99767) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of GRIP2 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–GRIP2 (Q9C0E4) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of WHRN is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–WHRN (Q9P202) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: CACNA1D-derived motif binding to a PDZ domain of GRIP1 is supported by the curated fragment-interaction record. Reason: PMID:36115835 measures binding between protein-derived PDZ-binding motifs and recombinant human PDZ domains by equilibrium holdup assays. GOA and the UniProt IntAct list both identify the exact CACNA1D–GRIP1 (Q9Y3R0) interaction. Together, the dedicated domain-binding assay framework and the curated target edge support refinement to PDZ domain binding. The main Results and selected Methods were read; the individual CACNA1D supplementary data row was not inspected. Therefore no target-specific affinity, domain number, motif sequence, orthogonal validation, full-length native interaction, or effect on channel physiology is asserted. The listed correction repairs figure values/labels/layout and does not state that this target interaction was withdrawn. Proposed replacements: PDZ domain binding |
| GO:0005886 plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: CaV1.3 functions at the plasma membrane. Reason: The preserved mouse ortholog transfer agrees with independently established human channel currents; the precise donor localization experiment was not reconstructed. Supporting Evidence: GO_REF:0000107 file:human/CACNA1D/CACNA1D-uniprot.txt |
| GO:0005886 plasma membrane | ISS PMID:21859974 Defects in ankyrin-based membrane protein targeting pathways... | ACCEPT | Summary: CaV1.3 functions at the plasma membrane. Reason: PMID:21859974 directly examines CaV1.3 membrane targeting in mouse atrial myocytes and transfected primary fibroblasts, with human atrial expression and peptide-binding observations. This supports the conserved location without describing mouse images as human images. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-265645 | ACCEPT | Summary: CaV1.3 functions at the plasma membrane. Reason: The complete Reactome summary explicitly describes voltage-gated calcium influx across plasma membrane and identifies CaV1.3 in beta-cell secretion. The preserved event-derived compartment assertion is also independently supported by human channel recordings. Supporting Evidence: Reactome:R-HSA-265645 file:human/CACNA1D/CACNA1D-uniprot.txt |
| GO:0005891 voltage-gated calcium channel complex | IBA GO_REF:0000033 | ACCEPT | Summary: Alpha1D is the pore-forming member of a voltage-gated calcium-channel complex. Reason: The PAINT ancestral-node assertion agrees with direct human channel reconstitution. The target among WITH/FROM sources is legitimate descendant experimental grounding, not circularity; the exact node placement was not independently reconstructed. Auxiliary subunits modulate the channel unit; their functions are not assigned to the alpha1D pore. |
| GO:0005891 voltage-gated calcium channel complex | IDA PMID:11160515 Biophysical properties, pharmacology, and modulation of huma... | ACCEPT | Summary: Alpha1D is the pore-forming member of a voltage-gated calcium-channel complex. Reason: PMID:11160515 expresses human alpha1D with alpha2delta1 and beta3a in HEK293 cells and measures the resulting channel currents. Auxiliary subunits modulate the channel unit; their functions are not assigned to the alpha1D pore. |
| GO:0005891 voltage-gated calcium channel complex | IEA GO_REF:0000120 | ACCEPT | Summary: Alpha1D is the pore-forming member of a voltage-gated calcium-channel complex. Reason: The combined ARBA/InterPro inference agrees with experimentally reconstituted alpha1D-containing channels. Auxiliary subunits modulate the channel unit; their functions are not assigned to the alpha1D pore. |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000002 | MODIFY | Summary: The broad transport term can be refined to calcium import across plasma membrane. Reason: Human alpha1D channels conduct extracellular calcium into the cytosol. The verified GO:0098703 definition describes that exact transport step, already represented in the source set; this is refinement rather than a new process. Proposed replacements: calcium ion import across plasma membrane |
| GO:0006816 calcium ion transport | IDA PMID:11160515 Biophysical properties, pharmacology, and modulation of huma... | ACCEPT | Summary: Human alpha1D directly mediates calcium transport. Reason: PMID:11160515 measures calcium- and barium-carried channel currents in a defined human alpha1D expression system. Calcium transport is the pore function; barium used as an experimental charge carrier is not asserted as physiological cargo. Supporting Evidence: |
| GO:0006936 muscle contraction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The broad muscle-contraction role is retained in its cardiac excitation context. Reason: The ARBA process is compatible with CaV1.3-dependent pacemaker and atrial electrical activity that organizes cardiac contraction. Human SANDD and mouse atrial channel studies support this context, but alpha1D is not generalized to the dominant ventricular or skeletal excitation-contraction channel. |
| GO:0007154 cell communication | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cell communication is a broad consequence of the channel's electrical and secretory roles. Reason: Calcium entry through CaV1.3 couples depolarization to auditory neurotransmitter release and endocrine secretion. Retain this broad existing inference outside the more informative channel core rather than treating it as a distinct signaling enzyme. |
| GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway | ISS GO_REF:0000024 | UNDECIDED | Summary: The precise adenylate-cyclase-modulating GPCR pathway assertion remains unresolved. Reason: The mouse Q99246-based ISS record is preserved, but the donor experiment establishing this pathway was not inspected. PMID:11160515 reports lack of modulation by selected Gi/o-linked receptors in a human heterologous preparation; this neither demonstrates every possible GPCR pathway nor disproves a distinct native signaling context. A calcium-channel current alone does not identify the direction or cyclase component of the asserted pathway. |
| GO:0007605 sensory perception of sound | IMP PMID:21131953 Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy... | ACCEPT | Summary: CaV1.3 calcium entry supports synaptic encoding of sound. Reason: The complete PMID:21131953 abstract explicitly links sound-induced hair-cell depolarization to neurotransmitter release through CaV1.3 and reports human deafness with a nonconducting channel variant. The channel supplies presynaptic calcium; its direct signaling role is distinguished from the initial mechanotransduction of hair-bundle movement. Full paper and images were not independently inspected. Supporting Evidence: PMID:21131953 translate sound-induced depolarization into neurotransmitter release in auditory hair cells |
| GO:0008092 cytoskeletal protein binding | IEA GO_REF:0000117 | MODIFY | Summary: The broad cytoskeletal-binding inference can be refined to alpha-actinin binding. Reason: PMID:17110593 explicitly reports CaV1.3 association with alpha-actinin2 and its bridging relationship to SK2. GO:0051393 is already present as an experimental target annotation and resolves the partner class more precisely. The cytoskeletal bridge belongs to alpha-actinin2; no adapter activity is transferred to the channel. Proposed replacements: alpha-actinin binding |
| GO:0008331 high voltage-gated calcium channel activity | IDA PMID:1309651 Structure and functional expression of alpha 1, alpha 2, and... | ACCEPT | Summary: CaV1.3 is an L-type member of the high-voltage-activated calcium-channel family. Reason: The official GO:0008331 includes L-type channels. Human alpha1D reconstitution in PMID:1309651 and the voltage dependence/pharmacology in PMID:11160515 independently establish this classification. Relatively negative activation compared with CaV1.2 and splice-dependent shifts do not change that family assignment. The original contributes_to qualifier is preserved. |
| GO:0008331 high voltage-gated calcium channel activity | IEA GO_REF:0000107 | ACCEPT | Summary: CaV1.3 is an L-type member of the high-voltage-activated calcium-channel family. Reason: The official GO:0008331 includes L-type channels. Human alpha1D reconstitution in PMID:1309651 and the voltage dependence/pharmacology in PMID:11160515 independently establish this classification. Relatively negative activation compared with CaV1.2 and splice-dependent shifts do not change that family assignment. The original enables qualifier is preserved. |
| GO:0010959 regulation of metal ion transport | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad regulation of ion transport is retained in the channel-coupling context. Reason: The existing ARBA process is supported at broad scope by calcium entry through CaV1.3 influencing SK2 potassium-channel function through local calcium signaling. It is less informative than direct calcium import and does not assign potassium conductance to alpha1D. |
| GO:0016020 membrane | EXP PMID:18482979 Modulation of voltage- and Ca2+-dependent gating of CaV1.3 L... | MODIFY | Summary: The broad membrane location can be refined to plasma membrane. Reason: Human channel electrophysiology and CaV1.3 membrane-targeting experiments establish the functional plasma-membrane pool. Intracellular biosynthetic pools are not excluded, and the original machine term is preserved. PMID:18482979 uses defined human channel splice constructs in HEK cells, rather than an endogenous localization assay for every product. Proposed replacements: plasma membrane |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: The broad membrane location can be refined to plasma membrane. Reason: Human channel electrophysiology and CaV1.3 membrane-targeting experiments establish the functional plasma-membrane pool. Intracellular biosynthetic pools are not excluded, and the original machine term is preserved. PMID:18482979 uses defined human channel splice constructs in HEK cells, rather than an endogenous localization assay for every product. Proposed replacements: plasma membrane |
| GO:0030018 Z disc | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific Z-disc assignment is not resolved by the inspected evidence. Reason: The mouse Q99246 transfer is preserved. Available CaV1.3 evidence establishes membrane targeting and alpha-actinin-mediated coupling, but binding a Z-disc protein is not itself proof of channel placement at that precise structure. The donor localization experiment and relevant images were not inspected. This is an access limitation, not a claim that orthology is invalid. |
| GO:0030018 Z disc | ISS GO_REF:0000024 | UNDECIDED | Summary: The specific Z-disc assignment is not resolved by the inspected evidence. Reason: The mouse Q99246 transfer is preserved. Available CaV1.3 evidence establishes membrane targeting and alpha-actinin-mediated coupling, but binding a Z-disc protein is not itself proof of channel placement at that precise structure. The donor localization experiment and relevant images were not inspected. This is an access limitation, not a claim that orthology is invalid. |
| GO:0030315 T-tubule | IEA GO_REF:0000117 | UNDECIDED | Summary: The fine T-tubule compartment is unresolved for this target in the inspected primary evidence. Reason: The ARBA assignment is preserved. PMID:21859974 supports atrial CaV1.3 membrane localization, but its inspected text does not independently resolve a T-tubular pool. The generic L-type complex ontology relation is not substituted for a target-specific localization assay. Native tissue and isoform context remain open. |
| GO:0030506 ankyrin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ankyrin binding helps organize CaV1.3 membrane targeting. Reason: Selected primary PMID:21859974 Results directly test CaV1.3 cytoplasmic fragments with ankyrin-B, map a conserved binding motif, and recover endogenous ankyrin-B from human atrial lysates with a motif peptide. Mouse atrial/fibroblast assays address targeting. Preserve the original mouse ortholog transfer; no claim is made that every assay used the canonical human sequence or that ankyrin-dependent targeting is the only route. |
| GO:0030506 ankyrin binding | ISS PMID:21859974 Defects in ankyrin-based membrane protein targeting pathways... | KEEP AS NON CORE | Summary: Ankyrin binding helps organize CaV1.3 membrane targeting. Reason: Selected primary PMID:21859974 Results directly test CaV1.3 cytoplasmic fragments with ankyrin-B, map a conserved binding motif, and recover endogenous ankyrin-B from human atrial lysates with a motif peptide. Mouse atrial/fibroblast assays address targeting. Preserve the original rat CaV1.3 P27732 ortholog-donor provenance; no claim is made that every assay used the canonical human sequence or that ankyrin-dependent targeting is the only route. Supporting Evidence: PMID:21859974 direct and specific interaction between AnkB membrane-binding domain and the C-terminal domain of Cav1.3 file:human/CACNA1D/CACNA1D-uniprot.txt |
| GO:0045762 positive regulation of adenylate cyclase activity | ISS GO_REF:0000024 | UNDECIDED | Summary: The direction of adenylate-cyclase regulation remains unresolved. Reason: The exact Q99246 ISS source is retained. Calcium influx could participate in calcium-sensitive cyclase regulation, but the donor assay establishing positive regulation was not inspected. Channel modulation by cAMP/PKA would not by itself prove the reverse causal direction. No absence of cyclase catalytic activity is used to reject a regulatory role. Supporting Evidence: GO_REF:0000024 file:human/CACNA1D/CACNA1D-uniprot.txt |
| GO:0048787 presynaptic active zone membrane | IEA GO_REF:0000107 | ACCEPT | Summary: CaV1.3 functions in presynaptic active-zone calcium entry in hair cells. Reason: The conserved mouse annotation agrees with the explicit hair-cell transmitter-release mechanism described in PMID:21131953. It is retained with curator deference for the precise donor localization record, whose original images were not re-examined. The active membrane channel is distinguished from vesicle-lumen content. |
| GO:0050877 nervous system process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The broad nervous-system process is retained outside the more specific channel mechanism. Reason: CaV1.3 contributes calcium entry to neuronal excitability and auditory signaling. Human channel recordings, splice-dependent gating and human loss-of-function phenotypes support the broad inference; variant-associated neurodevelopmental phenotypes are not treated as direct proof of every neuronal process. |
| GO:0051050 positive regulation of transport | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad regulation of ion transport is retained in the channel-coupling context. Reason: The existing ARBA process is supported at broad scope by calcium entry through CaV1.3 influencing SK2 potassium-channel function through local calcium signaling. It is less informative than direct calcium import and does not assign potassium conductance to alpha1D. |
| GO:0051393 alpha-actinin binding | IPI PMID:17110593 Molecular coupling of a Ca2+-activated K+ channel to L-type ... | KEEP AS NON CORE | Summary: CaV1.3 binds alpha-actinin2 as part of local channel organization. Reason: The complete PMID:17110593 abstract explicitly distinguishes alpha-actinin2 binding from direct SK2-CaV1.3 interaction. Alpha-actinin2 brings the channels together, allowing calcium entry to regulate SK2. Preserve the exact human P35609 partner assertion and defer to curation for uninspected full target assay details; native cardiac and deletion experiments are not represented as endogenous human assays. Supporting Evidence: PMID:17110593 colocalize via their interaction with alpha-actinin2 cytoskeletal protein |
| GO:0051928 positive regulation of calcium ion transport | IDA PMID:1309651 Structure and functional expression of alpha 1, alpha 2, and... | ACCEPT | Summary: Functional channel expression increases calcium entry. Reason: Retain the experimental curator's positive-regulation assertion for alpha1D-dependent calcium entry. PMID:1309651 establishes that human alpha1D coexpressed with beta2 and alpha2b produces a functional, voltage-dependent L-type calcium channel in Xenopus oocytes, providing positive functional evidence for channel-dependent control of calcium entry. The regulation framing is retained on the curator's assessment of the full experiment; the inspected abstract does not independently resolve the particular regulatory comparison underlying the IDA annotation. The existing calcium-import annotations separately describe ion movement through the channel, while this retained biological-process assertion records the curated enhancement of that transport. Supporting Evidence: |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: The broad transport term can be refined to calcium import across plasma membrane. Reason: Human alpha1D channels conduct extracellular calcium into the cytosol. The verified GO:0098703 definition describes that exact transport step, already represented in the source set; this is refinement rather than a new process. Proposed replacements: calcium ion import across plasma membrane |
| GO:0060372 regulation of atrial cardiac muscle cell membrane repolarization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CaV1.3-dependent local calcium signaling contributes to atrial repolarization. Reason: The exact mouse transfer is preserved and is independently consistent with PMID:17110593: CaV1.3 loss perturbs SK2 function and prolongs atrial repolarization. CaV1.3 supplies the calcium signal; SK2 conducts the repolarizing potassium current. The original donor record and every target image were not re-examined. |
| GO:0060372 regulation of atrial cardiac muscle cell membrane repolarization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CaV1.3-dependent local calcium signaling contributes to atrial repolarization. Reason: The exact mouse transfer is preserved and is independently consistent with PMID:17110593: CaV1.3 loss perturbs SK2 function and prolongs atrial repolarization. CaV1.3 supplies the calcium signal; SK2 conducts the repolarizing potassium current. The original donor record and every target image were not re-examined. |
| GO:0070509 calcium ion import | IDA PMID:1309651 Structure and functional expression of alpha 1, alpha 2, and... | ACCEPT | Summary: Alpha1D directly carries extracellular calcium across the plasma membrane. Reason: The human alpha1D reconstitution in PMID:1309651 establishes inward calcium-channel activity. The work performed by the protein is calcium movement through its pore. |
| GO:0070588 calcium ion transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: Alpha1D directly carries extracellular calcium across the plasma membrane. Reason: The InterPro-derived transport inference agrees with directly measured human alpha1D channel currents. The work performed by the protein is calcium movement through its pore. |
| GO:0070588 calcium ion transmembrane transport | ISS GO_REF:0000024 | ACCEPT | Summary: Alpha1D directly carries extracellular calcium across the plasma membrane. Reason: The exact mouse ortholog transfer is independently corroborated by human alpha1D reconstitution. The work performed by the protein is calcium movement through its pore. |
| GO:0086002 cardiac muscle cell action potential involved in contraction | IMP PMID:21131953 Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy... | ACCEPT | Summary: CaV1.3 current contributes to cardiac electrical excitation that supports contraction. Reason: The human SANDD paper couples a nonconducting channel to pronounced sinoatrial dysfunction, while the inspected atrial work independently links CaV1.3 membrane current to action-potential duration. Retain the existing cardiac process without describing CaV1.3 as the dominant ventricular excitation-contraction channel. |
| GO:0086007 voltage-gated calcium channel activity involved in cardiac muscle cell action potential | IC PMID:21859974 Defects in ankyrin-based membrane protein targeting pathways... | ACCEPT | Summary: CaV1.3 supplies depolarizing calcium current during cardiac action potentials. Reason: The inspected PMID:21859974 combines mouse atrial currents/action potentials, CaV1.3 targeting/binding and human atrial observations. Computational modeling helps explain the action-potential effect and is distinguished from the actual recordings. The original inference is consistent with the target channel's direct electrical work; no gap-junction or potassium-pore activity is assigned. |
| GO:0086007 voltage-gated calcium channel activity involved in cardiac muscle cell action potential | IEA GO_REF:0000117 | ACCEPT | Summary: CaV1.3 supplies depolarizing calcium current during cardiac action potentials. Reason: The inspected PMID:21859974 combines mouse atrial currents/action potentials, CaV1.3 targeting/binding and human atrial observations. Computational modeling helps explain the action-potential effect and is distinguished from the actual recordings. The original inference is consistent with the target channel's direct electrical work; no gap-junction or potassium-pore activity is assigned. |
| GO:0086012 membrane depolarization during cardiac muscle cell action potential | IC PMID:21859974 Defects in ankyrin-based membrane protein targeting pathways... | ACCEPT | Summary: CaV1.3 supplies depolarizing calcium current during cardiac action potentials. Reason: The inspected PMID:21859974 combines mouse atrial currents/action potentials, CaV1.3 targeting/binding and human atrial observations. Computational modeling helps explain the action-potential effect and is distinguished from the actual recordings. The original inference is consistent with the target channel's direct electrical work; no gap-junction or potassium-pore activity is assigned. |
| GO:0086046 membrane depolarization during SA node cell action potential | IMP PMID:21131953 Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy... | ACCEPT | Summary: CaV1.3 calcium current supports sinoatrial depolarization and heart-rate control. Reason: The complete PMID:21131953 abstract explicitly describes control of mouse SAN diastolic depolarization and a human nonconducting-channel syndrome with pronounced SAN dysfunction. The existing target assertion is retained with this convergent functional/clinical support and curator deference; a direct human SAN-cell recording is not claimed. The lower activation range within L-type channels provides the relevant inward-current mechanism. |
| GO:0086059 voltage-gated calcium channel activity involved SA node cell action potential | IEA GO_REF:0000107 | ACCEPT | Summary: CaV1.3 calcium current supports sinoatrial depolarization and heart-rate control. Reason: The complete PMID:21131953 abstract explicitly describes control of mouse SAN diastolic depolarization and a human nonconducting-channel syndrome with pronounced SAN dysfunction. The existing target assertion is retained with this convergent functional/clinical support and curator deference; a direct human SAN-cell recording is not claimed. The lower activation range within L-type channels provides the relevant inward-current mechanism. |
| GO:0086059 voltage-gated calcium channel activity involved SA node cell action potential | IMP PMID:21131953 Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy... | ACCEPT | Summary: CaV1.3 calcium current supports sinoatrial depolarization and heart-rate control. Reason: The complete PMID:21131953 abstract explicitly describes control of mouse SAN diastolic depolarization and a human nonconducting-channel syndrome with pronounced SAN dysfunction. The existing target assertion is retained with this convergent functional/clinical support and curator deference; a direct human SAN-cell recording is not claimed. The lower activation range within L-type channels provides the relevant inward-current mechanism. |
| GO:0086091 regulation of heart rate by cardiac conduction | IMP PMID:21131953 Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy... | ACCEPT | Summary: CaV1.3 calcium current supports sinoatrial depolarization and heart-rate control. Reason: The complete PMID:21131953 abstract explicitly describes control of mouse SAN diastolic depolarization and a human nonconducting-channel syndrome with pronounced SAN dysfunction. The existing target assertion is retained with this convergent functional/clinical support and curator deference; a direct human SAN-cell recording is not claimed. The lower activation range within L-type channels provides the relevant inward-current mechanism. |
| GO:0098681 synaptic ribbon | IEA GO_REF:0000107 | UNDECIDED | Summary: Activity associated with the synaptic ribbon requires a finer localization check. Reason: The official GO:0098681 denotes the electron-dense membraneless ribbon, whereas the well-supported channel mechanism operates in the adjacent presynaptic membrane. The original is_active_in assertion is preserved, and channel proximity is not treated as proof of structural membership. The exact mouse donor localization evidence was not inspected, so the assertion remains unresolved rather than being removed on topology alone. |
| GO:0098683 cochlear hair cell ribbon synapse | IEA GO_REF:0000107 | ACCEPT | Summary: CaV1.3 participates in calcium signaling at cochlear hair-cell ribbon synapses. Reason: PMID:21131953 explicitly connects hair-cell depolarization to neurotransmitter release and describes deafness caused by a nonconducting human channel. Retain the conserved mouse synaptic-context annotation; the exact donor images and a human ribbon-localization experiment were not independently examined. |
| GO:0098703 calcium ion import across plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Alpha1D directly carries extracellular calcium across the plasma membrane. Reason: The PAINT PTN001295293 assertion agrees with direct human channel function. A short donor list containing a fungal channel does not by itself undermine the ancestral-node inference; exact node placement was not reconstructed. The work performed by the protein is calcium movement through its pore. |
| GO:0099509 regulation of presynaptic cytosolic calcium ion concentration | IEA GO_REF:0000108 | ACCEPT | Summary: Presynaptic calcium entry through CaV1.3 couples depolarization to transmitter release. Reason: The original logical or mouse-ortholog inference agrees with the hair-cell channel mechanism described in PMID:21131953. Alpha1D performs the calcium-entry step and changes local cytosolic calcium; it is not merely a downstream requirement for release. The exact donor record and inference implementation were not independently reconstructed. |
| GO:0099626 voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic calcium levels | IEA GO_REF:0000107 | ACCEPT | Summary: Presynaptic calcium entry through CaV1.3 couples depolarization to transmitter release. Reason: The original logical or mouse-ortholog inference agrees with the hair-cell channel mechanism described in PMID:21131953. Alpha1D performs the calcium-entry step and changes local cytosolic calcium; it is not merely a downstream requirement for release. The exact donor record and inference implementation were not independently reconstructed. |
| GO:1901379 regulation of potassium ion transmembrane transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Local CaV1.3 calcium entry regulates SK2 potassium-channel function. Reason: The complete PMID:17110593 abstract explicitly reports alpha-actinin2-mediated channel coupling and defective SK2 function after CaV1.3 deletion. This supports potassium-transport regulation as a contextual signaling consequence without transferring potassium-pore activity or direct SK2 binding to alpha1D. Preserve the original mouse transfer. |
| GO:1901379 regulation of potassium ion transmembrane transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Local CaV1.3 calcium entry regulates SK2 potassium-channel function. Reason: The complete PMID:17110593 abstract explicitly reports alpha-actinin2-mediated channel coupling and defective SK2 function after CaV1.3 deletion. This supports potassium-transport regulation as a contextual signaling consequence without transferring potassium-pore activity or direct SK2 binding to alpha1D. Preserve the original mouse transfer. |
| GO:1990454 L-type voltage-gated calcium channel complex | IDA PMID:1309651 Structure and functional expression of alpha 1, alpha 2, and... | ACCEPT | Summary: Alpha1D forms the pore-bearing unit of an L-type calcium-channel complex. Reason: The complete PMID:1309651 abstract directly reports human alpha1D reconstitution with beta2 and alpha2b in Xenopus oocytes. The experimentally required auxiliary combination is specific to that system; it is not asserted as the sole assembly in every native tissue. Supporting Evidence: PMID:1309651 dihydropyridine-sensitive L-type Ca2+ channel when coexpressed with the beta |
Loading supporting content…
Download this section (compressed HTML)Q: Which donor experiments resolve positive adenylate-cyclase regulation and the specific GPCR pathway, distinguishing calcium-to-cAMP feedback from cAMP-dependent modulation of the channel?
Q: Which native tissues and splice products support the precise Z-disc, T-tubule and synaptic-ribbon assignments, as distinct from nearby plasma-membrane channel pools?
Q: How do the four named human products and additional C-terminal splice variants partition channel gating and partner binding among auditory, pacemaker, neuronal and endocrine cells?
Experiment: Compare defined human CaV1.3 splice products in matched pacemaker and sensory-cell models, measuring surface abundance, calcium-dependent and voltage-dependent inactivation, and coupled secretion with validated endogenous localization controls.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)