CACNB3

UniProt ID: P54284
Organism: Homo sapiens
Review Status: IN PROGRESS
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Gene Description

CACNB3 encodes the cytoplasmic beta3 regulatory subunit of voltage-gated calcium channels. Its SH3–guanylate-kinase-like module binds pore-forming alpha subunits, modulates channel gating and supports functional surface expression, influencing calcium influx in excitable cells.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005245 voltage-gated calcium channel activity
IDA
PMID:11160515
Biophysical properties, pharmacology, and modulation of huma...
MODIFY
Summary: Beta3 regulates the pore-forming alpha subunit. Coexpression establishes a contribution to channel activity, while calcium channel regulator activity specifies the beta-subunit mechanism.
Reason: Beta3 regulates the pore-forming alpha subunit. Coexpression establishes a contribution to channel activity, while calcium channel regulator activity specifies the beta-subunit mechanism.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0005245 voltage-gated calcium channel activity
IEA
GO_REF:0000120
MODIFY
Summary: Beta3 regulates the pore-forming alpha subunit. Coexpression establishes a contribution to channel activity, while calcium channel regulator activity specifies the beta-subunit mechanism.
Reason: Beta3 regulates the pore-forming alpha subunit. Coexpression establishes a contribution to channel activity, while calcium channel regulator activity specifies the beta-subunit mechanism.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0005245 voltage-gated calcium channel activity
TAS
PMID:8119293
Cloning, chromosomal location and functional expression of t...
MODIFY
Summary: Beta3 regulates the pore-forming alpha subunit. Coexpression establishes a contribution to channel activity, while calcium channel regulator activity specifies the beta-subunit mechanism.
Reason: Beta3 regulates the pore-forming alpha subunit. Coexpression establishes a contribution to channel activity, while calcium channel regulator activity specifies the beta-subunit mechanism.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0005246 calcium channel regulator activity
ISS
GO_REF:0000024
ACCEPT
Summary: Human beta3 coexpression modulates L-type channel currents; regulation is its direct molecular role.
Reason: Human beta3 coexpression modulates L-type channel currents; regulation is its direct molecular role.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0005246 calcium channel regulator activity
ISS
PMID:25527503
Functional characterization of CaVΞ±2Ξ΄ mutations associated w...
ACCEPT
Summary: Human beta3 coexpression modulates L-type channel currents; regulation is its direct molecular role.
Reason: Human beta3 coexpression modulates L-type channel currents; regulation is its direct molecular role.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0005515 protein binding
IPI
PMID:18535142
Calmodulin-dependent gating of Ca(v)1.2 calcium channels in ...
KEEP AS NON CORE
Summary: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
Reason: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
Reason: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
Reason: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
Reason: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
Reason: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
Reason: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
Reason: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
Reason: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
Reason: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
KEEP AS NON CORE
Summary: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
Reason: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
GO:0005515 protein binding
IPI
PMID:37207277
Using brain cell-type-specific protein interactomes to inter...
KEEP AS NON CORE
Summary: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
Reason: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func...
KEEP AS NON CORE
Summary: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
Reason: The physical interaction is retained, but generic protein binding does not specify the channel-regulatory mechanism. The high-throughput interaction is not used as proof of an additional enzymatic function.
GO:0005737 cytoplasm
EXP
PMID:34234349
Structure of human Ca(v)2.2 channel blocked by the painkille...
UNDECIDED
Summary: The cited experimental publication is not accessible in the local cache after the retrieval attempt; its specific cytoplasmic-localization observation remains unresolved.
Reason: The cited experimental publication is not accessible in the local cache after the retrieval attempt; its specific cytoplasmic-localization observation remains unresolved.
GO:0005737 cytoplasm
IEA
GO_REF:0000044
ACCEPT
Summary: CACNB3 is an intracellular accessory subunit acting on the cytoplasmic face of the calcium-channel complex.
Reason: CACNB3 is an intracellular accessory subunit acting on the cytoplasmic face of the calcium-channel complex.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0005829 cytosol
TAS
Reactome:R-HSA-210420
ACCEPT
Summary: The beta subunit is a cytosolic regulator that associates with intracellular portions of channel alpha subunits.
Reason: The beta subunit is a cytosolic regulator that associates with intracellular portions of channel alpha subunits.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0005891 voltage-gated calcium channel complex
IBA
GO_REF:0000033
ACCEPT
Summary: Reconstitution experiments place human beta3 in functional calcium-channel complexes.
Reason: Reconstitution experiments place human beta3 in functional calcium-channel complexes.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0005891 voltage-gated calcium channel complex
IDA
PMID:11160515
Biophysical properties, pharmacology, and modulation of huma...
ACCEPT
Summary: Reconstitution experiments place human beta3 in functional calcium-channel complexes.
Reason: Reconstitution experiments place human beta3 in functional calcium-channel complexes.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0005891 voltage-gated calcium channel complex
IEA
GO_REF:0000120
ACCEPT
Summary: Reconstitution experiments place human beta3 in functional calcium-channel complexes.
Reason: Reconstitution experiments place human beta3 in functional calcium-channel complexes.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0005891 voltage-gated calcium channel complex
TAS
PMID:8119293
Cloning, chromosomal location and functional expression of t...
ACCEPT
Summary: Reconstitution experiments place human beta3 in functional calcium-channel complexes.
Reason: Reconstitution experiments place human beta3 in functional calcium-channel complexes.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0006816 calcium ion transport
IBA
GO_REF:0000033
ACCEPT
Summary: Beta3 participates in calcium-ion transport by regulating functional channel complexes; it need not itself form the pore.
Reason: Beta3 participates in calcium-ion transport by regulating functional channel complexes; it need not itself form the pore.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0006816 calcium ion transport
IDA
PMID:11160515
Biophysical properties, pharmacology, and modulation of huma...
ACCEPT
Summary: Beta3 participates in calcium-ion transport by regulating functional channel complexes; it need not itself form the pore.
Reason: Beta3 participates in calcium-ion transport by regulating functional channel complexes; it need not itself form the pore.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0008331 high voltage-gated calcium channel activity
IBA
GO_REF:0000033
MODIFY
Summary: The high-voltage-activated channel is a multimeric assembly. Calcium channel regulator activity captures the beta3 subunit-specific role.
Reason: The high-voltage-activated channel is a multimeric assembly. Calcium channel regulator activity captures the beta3 subunit-specific role.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0016020 membrane
IDA
PMID:16525042
Alternative splicing of the voltage-gated Ca2+ channel beta4...
ACCEPT
Summary: Association with membrane channel complexes is consistent with membrane proteomics; this does not imply a transmembrane beta subunit.
Reason: Association with membrane channel complexes is consistent with membrane proteomics; this does not imply a transmembrane beta subunit.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0030315 T-tubule
IEA
GO_REF:0000117
UNDECIDED
Summary: The cited reviews discuss calcium-channel organization, but the evidence needed to assign a T-tubule location specifically to beta3 has not been isolated here. This is not a rejection based on a paper foregrounding another subunit.
Reason: The cited reviews discuss calcium-channel organization, but the evidence needed to assign a T-tubule location specifically to beta3 has not been isolated here. This is not a rejection based on a paper foregrounding another subunit.
GO:0030315 T-tubule
NAS
PMID:27273705
Voltage-gated calcium channels and their auxiliary subunits:...
UNDECIDED
Summary: The cited reviews discuss calcium-channel organization, but the evidence needed to assign a T-tubule location specifically to beta3 has not been isolated here. This is not a rejection based on a paper foregrounding another subunit.
Reason: The cited reviews discuss calcium-channel organization, but the evidence needed to assign a T-tubule location specifically to beta3 has not been isolated here. This is not a rejection based on a paper foregrounding another subunit.
GO:0045933 positive regulation of muscle contraction
NAS
PMID:22982493
Ca(V)1.1: The atypical prototypical voltage-gated Ca²⁺ chann...
KEEP AS NON CORE
Summary: Regulation of calcium entry can affect contraction. This physiological outcome is contextual and does not replace channel regulation as the core molecular role.
Reason: Regulation of calcium entry can affect contraction. This physiological outcome is contextual and does not replace channel regulation as the core molecular role.
GO:0045933 positive regulation of muscle contraction
NAS
PMID:34072954
Mechanisms and Regulation of Cardiac Ca(V)1.2 Trafficking.
KEEP AS NON CORE
Summary: Regulation of calcium entry can affect contraction. This physiological outcome is contextual and does not replace channel regulation as the core molecular role.
Reason: Regulation of calcium entry can affect contraction. This physiological outcome is contextual and does not replace channel regulation as the core molecular role.
GO:0060402 calcium ion transport into cytosol
ISS
PMID:25527503
Functional characterization of CaVΞ±2Ξ΄ mutations associated w...
ACCEPT
Summary: Beta3-containing channel complexes support calcium entry into the cytosol; the subunit participates by regulating channel function.
Reason: Beta3-containing channel complexes support calcium entry into the cytosol; the subunit participates by regulating channel function.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0061577 calcium ion transmembrane transport via high voltage-gated calcium channel
ISS
GO_REF:0000024
ACCEPT
Summary: Functional beta3-containing high-voltage-activated channel complexes support this calcium-transport process.
Reason: Functional beta3-containing high-voltage-activated channel complexes support this calcium-transport process.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0061577 calcium ion transmembrane transport via high voltage-gated calcium channel
ISS
PMID:25527503
Functional characterization of CaVΞ±2Ξ΄ mutations associated w...
ACCEPT
Summary: Functional beta3-containing high-voltage-activated channel complexes support this calcium-transport process.
Reason: Functional beta3-containing high-voltage-activated channel complexes support this calcium-transport process.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0070588 calcium ion transmembrane transport
IDA
PMID:27481713
The Ξ±2Ξ΄-1 subunit remodels CaV1.2 voltage sensors and allows...
ACCEPT
Summary: Coexpression and electrophysiology establish participation of beta3 in functional transmembrane calcium transport.
Reason: Coexpression and electrophysiology establish participation of beta3 in functional transmembrane calcium transport.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0070588 calcium ion transmembrane transport
IEA
GO_REF:0000002
ACCEPT
Summary: Coexpression and electrophysiology establish participation of beta3 in functional transmembrane calcium transport.
Reason: Coexpression and electrophysiology establish participation of beta3 in functional transmembrane calcium transport.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0070588 calcium ion transmembrane transport
NAS
PMID:22982493
Ca(V)1.1: The atypical prototypical voltage-gated Ca²⁺ chann...
ACCEPT
Summary: Coexpression and electrophysiology establish participation of beta3 in functional transmembrane calcium transport.
Reason: Coexpression and electrophysiology establish participation of beta3 in functional transmembrane calcium transport.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0070588 calcium ion transmembrane transport
NAS
PMID:27273705
Voltage-gated calcium channels and their auxiliary subunits:...
ACCEPT
Summary: Coexpression and electrophysiology establish participation of beta3 in functional transmembrane calcium transport.
Reason: Coexpression and electrophysiology establish participation of beta3 in functional transmembrane calcium transport.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0072659 protein localization to plasma membrane
ISS
PMID:25527503
Functional characterization of CaVΞ±2Ξ΄ mutations associated w...
ACCEPT
Summary: CaV beta-subunit association supports channel surface expression, consistent with the conserved trafficking role of the SH3–GK module.
Reason: CaV beta-subunit association supports channel surface expression, consistent with the conserved trafficking role of the SH3–GK module.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:0098903 regulation of membrane repolarization during action potential
ISS
PMID:25527503
Functional characterization of CaVΞ±2Ξ΄ mutations associated w...
KEEP AS NON CORE
Summary: Calcium-channel regulation can influence action-potential repolarization in excitable cells, but the particular tissue and channel partner determine the effect.
Reason: Calcium-channel regulation can influence action-potential repolarization in excitable cells, but the particular tissue and channel partner determine the effect.
GO:1901843 positive regulation of high voltage-gated calcium channel activity
ISS
GO_REF:0000024
ACCEPT
Summary: The beta3 regulatory subunit supports functional high-voltage-activated channel activity in coexpression systems.
Reason: The beta3 regulatory subunit supports functional high-voltage-activated channel activity in coexpression systems.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:1990454 L-type voltage-gated calcium channel complex
IPI
PMID:27481713
The Ξ±2Ξ΄-1 subunit remodels CaV1.2 voltage sensors and allows...
ACCEPT
Summary: Human beta3 was included in functional L-type channel assemblies in the cited coexpression experiments.
Reason: Human beta3 was included in functional L-type channel assemblies in the cited coexpression experiments.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:1990454 L-type voltage-gated calcium channel complex
ISS
GO_REF:0000024
ACCEPT
Summary: Human beta3 was included in functional L-type channel assemblies in the cited coexpression experiments.
Reason: Human beta3 was included in functional L-type channel assemblies in the cited coexpression experiments.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:1990454 L-type voltage-gated calcium channel complex
ISS
GO_REF:0000114
ACCEPT
Summary: Human beta3 was included in functional L-type channel assemblies in the cited coexpression experiments.
Reason: Human beta3 was included in functional L-type channel assemblies in the cited coexpression experiments.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.
GO:1990454 L-type voltage-gated calcium channel complex
ISS
PMID:25527503
Functional characterization of CaVΞ±2Ξ΄ mutations associated w...
ACCEPT
Summary: Human beta3 was included in functional L-type channel assemblies in the cited coexpression experiments.
Reason: Human beta3 was included in functional L-type channel assemblies in the cited coexpression experiments.
Supporting Evidence:
PMID:8119293
The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.

Core Functions

Regulation of voltage-gated calcium-channel assembly, trafficking and gating.

Supporting Evidence:
  • PMID:8119293
    The cloned H beta 3 subunit was further expressed in Xenopus oocytes to demonstrate its ability to modulate VDCC activity.

References

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Deep Research

Falcon

(CACNB3-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(CACNB3-notes.md)

CACNB3: evidence notes

Paired horse benchmark evidence review

The human reference supplies mechanistic evidence for the corresponding selected horse protein; the human conclusion alone is not validation of the horse sequence. The exact horse comparison is in genes/HORSE/CACNB3/CACNB3-bioinformatics/RESULTS.md. Research reports are source leads; annotation decisions cite the underlying publication or experimentally supported UniProt passages. Unresolved source-specific results retain UNDECIDED.

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