CACNA1D encodes the pore-forming alpha1D subunit of CaV1.3. Human channel reconstitution establishes voltage-gated, dihydropyridine-sensitive calcium conductance, with auxiliary-subunit effects that depend on the expression system (PMID:1309651; PMID:11160515). CaV1.3 activates at relatively negative potentials within the L-type family; this does not make it a T-type channel. One channel core combines this molecular activity with calcium import, sinoatrial pacemaker depolarization and auditory neurotransmitter release. In the latter setting the channel supplies presynaptic calcium for synaptic encoding; it is not the mechanically gated sound-transduction channel (PMID:21131953).
Human loss-of-function and gain-of-function observations are distinguished from measurements in native mouse cells and heterologous expression systems. The complete PMID:21131953 abstract describes human SANDD families and nonconducting channels alongside mouse pacemaker and hair-cell mechanism context. Direct human sinoatrial-cell recording was not established by the material accessed. Primary variant studies demonstrate altered activation or inactivation, with peak-current effects varying among variants; reduced peak amplitude can coexist with persistent calcium entry (PMID:23913001; PMID:25620733; PMID:28472301). These experiments are not a new clinical disease-validity assessment or treatment recommendation.
C-terminal splicing modulates activation and calcium-dependent inactivation. PMID:18482979 uses a human channel backbone with a rat exon 42A sequence whose encoded amino acids match the human sequence, heterologous recordings, C-terminal fragments and FRET. Tissue expression and human RT-PCR are distinct from those functional assays. The later 43s construct in PMID:28472301 is not automatically identified with named product 42A. The four normal source mappings remain literal: Neuronal-type/Q01668-1; Beta-cell-type/Q01668-2; 4 (Ca(V)1.3(42A))/Q01668-4; and 3/Q01668-3, with their original sequence notes. Additional splice products can exist.
Twenty generic interaction assertions were refined to the domain-binding activity actually studied: the SHANK3-1 edge to SH3 domain binding, and 19 fragmentomics edges to PDZ domain binding. The complete SHANK abstract supports binding of Shank SH3 domains to a channel region; the exact human partner is preserved from GOA and UniProt (PMID:30058071). The fragmentomics study tests protein-derived motifs against recombinant human PDZ domains by equilibrium holdup assays (PMID:36115835). The exact curated positive edges, rather than the mere existence of a screen, identify the target interactions. Individual CACNA1D supplementary values, motif sequences, domain ordinals and pair-specific orthogonal validation were not inspected. No numerical affinity, native full-channel assembly or physiological function of each interaction is inferred.
The official correction to PMID:36115835 was read through the complete indexed publisher text; direct page access failed. It supplies omitted Figure 2 correlation values and axis labels, the omitted leftmost Figure 4a column, and Figure 5 labels/panel ordering. The publisher states that the PDF and HTML were corrected. Corrected images were not inspected. The notice does not state withdrawal of the CACNA1D interactions. This access boundary is also recorded in the reference assessment.
Ankyrin-dependent targeting and alpha-actinin-linked coupling to SK2 remain contextual binding functions rather than separate pore activities. PMID:21859974 includes mouse atrial/fibroblast assays, channel fragments and motif peptides, human atrial lysates and computational modeling. Rat CaV1.3 P27732 in the ISS assertion is an ortholog donor, not an ankyrin binding partner. Motif numbering is not silently transferred to the current human sequence. PMID:17110593 supports alpha-actinin2-mediated channel association and coupled atrial repolarization; it does not assign potassium conductance to CaV1.3.
Six decisions remain UNDECIDED: the precise G-protein-coupled adenylate-cyclase pathway, positive adenylate-cyclase regulation, two Z-disc assertions, a T-tubule assertion and the synaptic-ribbon assertion. The accessible evidence does not resolve those specific donor assays or fine locations. An ontology relation for the channel complex, partner binding or a trafficking phenotype is not substituted for a target localization assay. The official ribbon definition describes the membraneless ribbon structure; nearby presynaptic membrane localization alone does not settle the finer source assertion. These are unresolved claims, not declarations that the original curators were wrong.
All 78 source assertions, 19 original reference identities and four products were preserved. The decisions are 34 ACCEPT, 12 KEEP_AS_NON_CORE, 26 MODIFY and six UNDECIDED, with one integrated core and no NEW annotations. A normal UniProt source reference was added. Supported contextual interactions are retained in accordance with the standing project instruction; the domain-specific refinements use the actual assay scope rather than transferring partner activities.
All 11 canonical PMID abstracts and bibliographic records, the UniProt functional and product sections, and the complete Reactome calcium-influx summary were read. Selected primary Methods, Results and Discussion were read for PMID:18482979, PMID:21859974, PMID:23913001, PMID:25620733 and PMID:28472301. The bounded binding consultation independently inspected the PMID:36115835 assay framework and correction, and the accessible PMID:30058071 material. Its recommendations and source-access limits were read and integrated by the whole-review author. Abstract-only records and failed publisher access are identified per reference; no complete-paper or image-reading claim follows from a full-text cache flag. Existing canonical caches were preserved, including records with fetched metadata or whitespace variants.
One normal Falcon research invocation with the configured perplexity-lite fallback failed because DNS resolution was unavailable. No provider report was generated. This review therefore uses the cited primary records, curated source annotations and explicitly bounded manual reading. Fourteen short evidence anchors are exact substrings of the normal canonical caches; aggregate use, including repeated core anchors, is at most 25 words per source. No quotation was taken from an alternate cache, inaccessible figure or web-only correction.
Full normal validation, including references, GOA consistency and authored ontology terms, passed with no warnings. The COMPLETE status records completed assessment and successful checks; it does not erase the six explicit UNDECIDED decisions.
The independently approved review passed full normal canonical validation and status reporting without warnings. COMPLETE retains all six explicit UNDECIDED decisions. All 78 source assertions, four named products and source-cache bytes are preserved. The standard CREATE history record passed history validation.
The GO:0051928 IDA assertion from PMID:1309651(https://pubmed.ncbi.nlm.nih.gov/1309651/) remains ACCEPT. Its reason now states the basis for retaining the curator's positive-regulation interpretation and the limits of the independently inspected evidence. The complete cached abstract establishes functional reconstitution of human alpha1D with beta2 and alpha2b in Xenopus oocytes. Alpha1D alone, or with alpha2b alone, did not produce functional channel activity. These data support the channel assembly's control of calcium entry; the exact comparison that led the curator to use the regulation term was not independently inspected in full text. Direct PubMed access returned an empty page and the publisher DOI request was inaccessible, so neither the original figures nor the full experiment is claimed as read.
The current GO:0051928 definition and parents describe enhancement of calcium transport and place the term under positive ion-transport regulation and calcium-transport regulation, with a positively-regulates relation to calcium transport. Regulation is distinct from executing calcium import. Retention here therefore rests on the experimental annotation and compatible channel-function evidence, rather than treating every calcium-conducting pore as automatically carrying a regulation assertion. A separate molecular channel-activator function is not inferred.
The broader experimental calcium-transport annotations are retained on their source-specific experimental or phylogenetic evidence. The two generic InterPro transport mappings are refined to the already represented calcium-import term because they offer less process specificity. This distinction does not equate the regulation and import terms. The existing one-core synthesis, ribbon-localization uncertainty, all other 77 annotation reviews, all 78 source objects, four products, 20 references and 14 quotation entries remain unchanged. No new annotations, sources or quotation words are introduced.
The independently approved reason-only follow-up passed full normal canonical validation, status reporting, targeted rendering and standard EDIT history validation. COMPLETE remains unchanged. All source objects, products, references, earlier sources and history are preserved. See the follow-up history.