CACNA2D4

Summary: Retain the curated channel-activity assertion on the experimentally supported auxiliary function of alpha2delta-4.

Reason: PMID:12181424 reports that human alpha2delta-4 associates with CaV1.2/beta3 and enhances channel-mediated calcium influx. This corroborates the conserved functional role of the auxiliary subunit in a calcium-channel assembly. Retain the existing term with deference to the experimental curation; the separate regulator annotation specifies the subunit's own molecular work. Alpha1 supplies the pore. The original machine qualifier is preserved, and its source-level relation remains an unresolved audit question; neither retention nor the core asserts that a new contributes_to relation has been established. The PAINT ancestor PTN000018330 and descendant evidence are unchanged. Target self-inclusion is expected, and neither donor count nor an uninspected tree demonstrates propagation failure.

Summary: Retain the experimentally curated channel-activity assertion with alpha2delta-4 identified as an auxiliary regulator.

Reason: The complete PMID:12181424 abstract reports association of human alpha2delta-4 with CaV1.2/beta3 and increased channel-dependent calcium influx. These positive functional results support retaining the curator's term while identifying the subunit's own activity as calcium-channel regulation. The original full paper remains unavailable, so this review does not replace the experimental assertion solely because alpha2delta-4 is auxiliary. Alpha1 forms the pore; current GO relation guidance does not establish a new contributes_to assignment here. The machine qualifier remains unchanged and its source-level audit is unresolved. Native mouse evidence in PMID:28262416 and PMID:29875267 corroborates regulatory effects, with residual currents after deletion that preclude a universal necessity claim.

Summary: Alpha2delta-4 is an auxiliary component of voltage-gated calcium-channel complexes.

Reason: The conserved complex membership inferred by PAINT is independently consistent with direct association of human alpha2delta-4 with CaV1.2 and beta3 in PMID:12181424. The exact inherited ancestral placement is not reconstructed, but target evidence supports the asserted complex role.

Summary: Human alpha2delta-4 associates with pore-forming CaV1.2 and beta3 subunits.

Reason: The explicit association and enhancement of channel-dependent calcium influx reported in PMID:12181424 support membership in the voltage-gated calcium-channel complex. This is an auxiliary complex component, not a separate pore-forming channel.

Summary: Alpha2delta-4 is a membrane-associated calcium-channel auxiliary protein.

Reason: The UniProt subcellular-location mapping is consistent with its signal peptide, extracellular domain and C-terminal membrane anchor, as well as its channel-associated function. The broad membrane location is appropriate. It does not require assuming that predicted proteolysis or a particular alternative anchoring mechanism has been demonstrated.

Summary: CACNA2D4 is required for normal retinal function, but the specific light-detection step remains unresolved.

Reason: PMID:17033974 establishes human cone dystrophy and places the auxiliary subunit in photoreceptor ribbon-synapse calcium-channel function. GO:0050908 concerns receiving light and converting it into a molecular signal; impaired synaptic transmission can also disrupt visual responses downstream of that step. The accessible abstract and PubMed figure caption do not settle the exact experimental annotation, and the complete original article could not be accessed. Retain the curator assertion as unresolved rather than reject it from incomplete evidence. Later mouse evidence separates preserved photocurrents from impaired synaptic transmission (PMID:28262416); a small a-wave reduction in older mutants was considered alongside retinal degeneration (PMID:29875267). These findings support downstream function but do not resolve every assay in the inaccessible original human report.

Summary: The auxiliary alpha2delta-4 subunit participates in calcium transport by supporting the active channel complex.

Reason: PMID:12181424 directly demonstrates increased channel-mediated calcium influx when human alpha2delta-4 is coexpressed with CaV1.2 and beta3. Its active regulatory contribution to the transporting complex supports this process annotation. Ion passage occurs through alpha1, so the process assignment does not imply that alpha2delta-4 independently conducts calcium. The mouse studies PMID:28262416 and PMID:29875267 corroborate its functional contribution to native presynaptic calcium entry, with residual activity after loss of the auxiliary subunit.

Summary: Human alpha2delta-4 directly regulates calcium-channel activity as an associated auxiliary subunit.

Reason: The human coexpression/association and increased CaV1.2/beta3-mediated influx in PMID:12181424 establish the subunit's own regulatory activity. Native mouse current-density and voltage-sensitivity changes in PMID:28262416 provide corroborating physiological context, without converting mouse assays into native human evidence. GO:0005246 lies under ion channel regulator activity and is not an is_a ancestor or descendant of GO:0005245; it adds the regulator's own molecular work alongside the retained curated channel-activity assertion. The existing CACNA2D1 review illustrates the same role distinction, but the supporting experiment here is on human alpha2delta-4. No new biological-process claim is proposed.