CACNB4 calcium voltage-gated channel auxiliary subunit beta 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CACNB4provided by HGNC
Official Full Name: calcium voltage-gated channel auxiliary subunit beta 4provided by HGNC
Primary source: HGNC:HGNC:1404
See related: Ensembl:ENSG00000182389 MIM:601949; AllianceGenome:HGNC:1404
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EA5; EJM; CAB4; EIG9; EJM4; EJM6; CACNLB4
Summary: This gene encodes a member of the beta subunit family of voltage-dependent calcium channel complex proteins. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. The protein encoded by this locus plays an important role in calcium channel function by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation. Certain mutations in this gene have been associated with idiopathic generalized epilepsy (IGE), juvenile myoclonic epilepsy (JME), and episodic ataxia, type 5. [provided by RefSeq, Aug 2016]
Expression: Biased expression in brain (RPKM 5.9), skin (RPKM 2.0) and 8 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q23.3

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (151832771..152099167, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (152284205..152568400, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (152689285..152955681, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The homozygous CACNB4 p.(Leu126Pro) variant underlies the severe neurological phenotype in the two siblings.
Title: A homozygous missense variant in CACNB4 encoding the auxiliary calcium channel beta4 subunit causes a severe neurodevelopmental disorder and impairs channel and non-channel functions.
The nuclear targeting properties of the truncated beta(4b(1-481)) subunit in tsA-201 cells, skeletal myotubes, and in hippocampal neurons, were investigated.
Title: The juvenile myoclonic epilepsy mutant of the calcium channel β(4) subunit displays normal nuclear targeting in nerve and muscle cells.
Genome-wide association studies identify CACNB4 mutation releated to juvenile myoclonic epilepsy.
Title: The quest for juvenile myoclonic epilepsy genes.
Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy
Title: Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy.
The Ca2+ channel beta4c subunit interacts with heterochromatin protein 1 gama via a PXVXL binding motif.
Title: The Ca2+ channel beta4c subunit interacts with heterochromatin protein 1 via a PXVXL binding motif.
CACNB4 is associated with acute lung injury in mice
Title: Haplotype association mapping of acute lung injury in mice implicates activin a receptor, type 1.
proband identified with severe myoclonic epilepsy in infancy heterozygous for de novo SCN1A nonsense mutation & CACNB4 missense mutation (R468Q); greater Ca(v)2.1 currents caused by the mutation may increase neurotransmitter release in excitatory neurons
Title: A CACNB4 mutation shows that altered Ca(v)2.1 function may be a genetic modifier of severe myoclonic epilepsy in infancy.
No pathogenic mutation were identified in CACNB4.
Title: Episodic ataxia: SLC1A3 and CACNB4 do not explain the apparent genetic heterogeneity.
plays a role in neurotransmitter release.
Title: [Physiological role of presynaptic Ca2+ channel complexes on neurotransmitter release].
Observational study of gene-disease association. (HuGE Navigator)
Title: Replication of previous genome-wide association studies of bone mineral density in premenopausal American women.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Epilepsy, idiopathic generalized, susceptibility to, 9 MedGen: C2750887 OMIM: 607682 GeneReviews: Not available	Compare labs
Episodic ataxia type 5 MedGen: C1866039 OMIM: 613855 GeneReviews: Hereditary Ataxia Overview	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study of chemotherapy-induced alopecia in breast cancer patients. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D2S1751 (e-PCR)
- UniSTS:12553

WI-15038 (e-PCR)
- UniSTS:20517

SHGC-82083 (e-PCR)
- UniSTS:103012

SHGC-143363 (e-PCR)
- UniSTS:171883

SHGC-156047 (e-PCR)
- UniSTS:183436

SHGC-156071 (e-PCR)
- UniSTS:183438

SHGC-149129 (e-PCR)
- UniSTS:176816

SHGC-152741 (e-PCR)
- UniSTS:177596

NoName (e-PCR)
- UniSTS:481984

D2S2236 (e-PCR)
- UniSTS:40410

D2S1720E (e-PCR)
- UniSTS:150749

NoName (e-PCR)
- UniSTS:482288

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to high voltage-gated calcium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IEA Inferred from Electronic Annotation more info
contributes_to voltage-gated calcium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic calcium levels	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Peyer's patch development	IEA Inferred from Electronic Annotation more info
involved_in T cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in adult walking behavior	IEA Inferred from Electronic Annotation more info
involved_in cAMP metabolic process	IEA Inferred from Electronic Annotation more info
involved_in calcium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in calcium ion transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to leukemia inhibitory factor	IEA Inferred from Electronic Annotation more info
involved_in chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in detection of light stimulus involved in visual perception	IEA Inferred from Electronic Annotation more info
involved_in gamma-aminobutyric acid secretion	IEA Inferred from Electronic Annotation more info
involved_in gamma-aminobutyric acid signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in muscle cell development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of G1/S transition of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in neuromuscular junction development	IEA Inferred from Electronic Annotation more info
involved_in neuronal action potential propagation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein localization to nucleolus	IEA Inferred from Electronic Annotation more info
involved_in regulation of presynaptic cytosolic calcium ion concentration	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic vesicle exocytosis	IEA Inferred from Electronic Annotation more info
involved_in regulation of voltage-gated calcium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in spleen development	IEA Inferred from Electronic Annotation more info
involved_in synaptic transmission, glutamatergic	IEA Inferred from Electronic Annotation more info
involved_in thymus development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytoplasmic side of plasma membrane	TAS Traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in nuclear speck	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in presynapse	IEA Inferred from Electronic Annotation more info
located_in synapse	IDA Inferred from Direct Assay more info	PubMed
part_of voltage-gated calcium channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of voltage-gated calcium channel complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: voltage-dependent L-type calcium channel subunit beta-4

Names: calcium channel voltage-dependent subunit beta 4; dihydropyridine-sensitive L-type, calcium channel beta-4 subunit

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012641.1 RefSeqGene

Range

5036..271309

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000726.5 → NP_000717.2 voltage-dependent L-type calcium channel subunit beta-4 isoform b

See identical proteins and their annotated locations for NP_000717.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) encodes the longest isoform (b). This isoform has a b-type N-terminus.

Source sequence(s)

AC079790, AC097448, BC075049, T23939

Consensus CDS

CCDS46426.1

UniProtKB/Swiss-Prot

A7BJ74, A8K1Y4, B4DG40, O00305, O60515, Q6B000, Q96L40

UniProtKB/TrEMBL

A8K5R3

Related

ENSP00000438949.1, ENST00000539935.7

Conserved Domains (3) summary

cd12043
Location:91 → 158

SH3_CACNB4; Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta4

pfam00625
Location:218 → 398

Guanylate_kin; Guanylate kinase

pfam12052
Location:50 → 91

VGCC_beta4Aa_N; Voltage gated calcium channel subunit beta domain 4Aa N terminal
NM_001005746.4 → NP_001005746.1 voltage-dependent L-type calcium channel subunit beta-4 isoform c

See identical proteins and their annotated locations for NP_001005746.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and 5' coding region, compared to variant 2. The resulting isoform (c) has a shorter and distinct N-terminus, compared to isoform b.

Source sequence(s)

AC079790, AC097448, AK316045, T23939

Consensus CDS

CCDS46427.1

UniProtKB/TrEMBL

A8K5R3

Related

ENSP00000489677.1, ENST00000638005.1

Conserved Domains (3) summary

cd12043
Location:73 → 140

SH3_CACNB4; Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta4

pfam00625
Location:200 → 380

Guanylate_kin; Guanylate kinase

pfam12052
Location:32 → 73

VGCC_beta4Aa_N; Voltage gated calcium channel subunit beta domain 4Aa N terminal
NM_001005747.4 → NP_001005747.1 voltage-dependent L-type calcium channel subunit beta-4 isoform a

See identical proteins and their annotated locations for NP_001005747.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents use of an alternate promoter and 5' UTR and differs in the 5' coding region, compared to variant 2. The resulting isoform (a) has a shorter and distinct N-terminus, compared to isoform b. This isoform has an a-type N-terminus.

Source sequence(s)

AC068547, AC097448, AK290049, T23939

Consensus CDS

CCDS46428.1

UniProtKB/TrEMBL

A0A1B0GXG0

Related

ENSP00000443893.1, ENST00000534999.7

Conserved Domains (3) summary

cd12043
Location:57 → 124

SH3_CACNB4; Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta4

pfam00625
Location:184 → 364

Guanylate_kin; Guanylate kinase

pfam12052
Location:16 → 57

VGCC_beta4Aa_N; Voltage gated calcium channel subunit beta domain 4Aa N terminal
NM_001145798.2 → NP_001139270.1 voltage-dependent L-type calcium channel subunit beta-4 isoform d

See identical proteins and their annotated locations for NP_001139270.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate in-frame exon in the 3' coding region, compared to variant 2. The resulting isoform (d) lacks an internal segment near the C-terminus, compared to isoform b. This isoform has a b-type N-terminus.

Source sequence(s)

AB302276, AC079790, AC097448, T23939

Consensus CDS

CCDS54409.1

UniProtKB/TrEMBL

A0A1B0GTS4

Related

ENSP00000201943.5, ENST00000201943.10

Conserved Domains (3) summary

cd12043
Location:91 → 158

SH3_CACNB4; Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta4

pfam12052
Location:50 → 91

VGCC_beta4Aa_N; Voltage gated calcium channel subunit beta domain 4Aa N terminal

cl27059
Location:218 → 371

Guanylate_kin; Guanylate kinase
NM_001320722.3 → NP_001307651.1 voltage-dependent L-type calcium channel subunit beta-4 isoform e

Status: REVIEWED

Description

Transcript Variant: This variant (5) represents use of an alternate promoter and 5' UTR and differs in the 5' coding region, compared to variant 2. The resulting isoform (e) has a shorter and distinct N-terminus, compared to isoform b.

Source sequence(s)

AC068547, AC097448, AK316045, DA082068, DA782833

Consensus CDS

CCDS82522.1

UniProtKB/TrEMBL

A0A1B0GTX2, H0Y476

Related

ENSP00000490250.1, ENST00000637217.1

Conserved Domains (3) summary

cd12043
Location:44 → 111

SH3_CACNB4; Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta4

pfam00625
Location:171 → 351

Guanylate_kin; Guanylate kinase

pfam12052
Location:3 → 44

VGCC_beta4Aa_N; Voltage gated calcium channel subunit beta domain 4Aa N terminal
NM_001330113.2 → NP_001317042.1 voltage-dependent L-type calcium channel subunit beta-4 isoform f

Status: REVIEWED

Source sequence(s)

AC068547, AC079790, AC097448

UniProtKB/TrEMBL

A0A1B0GVU5

Related

ENSP00000489788.1, ENST00000636785.1
NM_001330114.2 → NP_001317043.1 voltage-dependent L-type calcium channel subunit beta-4 isoform g

Status: REVIEWED

Description

Transcript Variant: This variant (7) represents use of an alternate promoter compared to variant 2.

Source sequence(s)

AC068547, AC097448

UniProtKB/TrEMBL

Q580I4

Conserved Domains (1) summary

pfam00625
Location:1 → 180

Guanylate_kin; Guanylate kinase
NM_001330115.2 → NP_001317044.1 voltage-dependent L-type calcium channel subunit beta-4 isoform h

Status: REVIEWED

Description

Transcript Variant: This variant (8) represents use of an alternate promoter compared to variant 2. The encoded isoform (h) has an a-type N-terminus.

Source sequence(s)

AC068547, AC097448

Consensus CDS

CCDS82523.1

UniProtKB/TrEMBL

A0A1B0GTK1, A0A1B0GVU5

Related

ENSP00000489732.1, ENST00000637779.1
NM_001330116.2 → NP_001317045.1 voltage-dependent L-type calcium channel subunit beta-4 isoform i

Status: REVIEWED

Description

Transcript Variant: This variant (9) represents use of an alternate promoter compared to variant 2.

Source sequence(s)

AC068547, AC097448

Consensus CDS

CCDS82521.1

UniProtKB/TrEMBL

A0A1B0GTX8, A0A1B0GVU5

Related

ENSP00000489883.1, ENST00000638040.1
NM_001330117.2 → NP_001317046.1 voltage-dependent L-type calcium channel subunit beta-4 isoform j

Status: REVIEWED

Description

Transcript Variant: This variant (10) represents use of an alternate promoter compared to variant 2.

Source sequence(s)

AC068547, AC097448

Consensus CDS

CCDS82520.1

UniProtKB/TrEMBL

A0A1B0GTP5

Related

ENSP00000489787.1, ENST00000637284.1

Conserved Domains (1) summary

pfam00625
Location:32 → 212

Guanylate_kin; Guanylate kinase
NM_001330118.1 → NP_001317047.1 voltage-dependent L-type calcium channel subunit beta-4 isoform e

Status: REVIEWED

Description

Transcript Variant: This variant (11) represents use of an alternate promoter compared to variant 2.

Source sequence(s)

AC068547, AC097448

Consensus CDS

CCDS82522.1

UniProtKB/TrEMBL

A0A1B0GTX2, H0Y476

Related

ENSP00000390161.2, ENST00000439467.6

Conserved Domains (3) summary

cd12043
Location:44 → 111

SH3_CACNB4; Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta4

pfam00625
Location:171 → 351

Guanylate_kin; Guanylate kinase

pfam12052
Location:3 → 44

VGCC_beta4Aa_N; Voltage gated calcium channel subunit beta domain 4Aa N terminal

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

151832771..152099167 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011511797.4 → XP_011510099.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X3

UniProtKB/TrEMBL

A8K5R3

Conserved Domains (3) summary

cd12043
Location:91 → 158

SH3_CACNB4; Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta4

pfam12052
Location:50 → 91

VGCC_beta4Aa_N; Voltage gated calcium channel subunit beta domain 4Aa N terminal

cl17190
Location:230 → 336

NK; Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates ...
XM_047445790.1 → XP_047301746.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X1

UniProtKB/TrEMBL

A0A1B0GTX2, H0Y476
XM_047445791.1 → XP_047301747.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X4

UniProtKB/TrEMBL

A0A1B0GTP5
XM_011511796.3 → XP_011510098.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X2

See identical proteins and their annotated locations for XP_011510098.1

UniProtKB/TrEMBL

A0A1B0GTX2

Conserved Domains (4) summary

cd12043
Location:43 → 110

SH3_CACNB4; Src Homology 3 domain of Voltage-dependent L-type calcium channel subunit beta4

pfam00625
Location:170 → 350

Guanylate_kin; Guanylate kinase

pfam12052
Location:2 → 43

VGCC_beta4Aa_N; Voltage gated calcium channel subunit beta domain 4Aa N terminal

cl17190
Location:180 → 351

NK; Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates ...
XM_047445792.1 → XP_047301748.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X5

UniProtKB/TrEMBL

Q580I4
XM_047445794.1 → XP_047301750.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X7

UniProtKB/TrEMBL

A0A1B0GUI8
XM_047445798.1 → XP_047301754.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X12

UniProtKB/TrEMBL

A0A1B0GUU8, E7DBM8, F8WA06

Related

ENSP00000490510.1, ENST00000637491.1
XM_047445797.1 → XP_047301753.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X10
XM_047445795.1 → XP_047301751.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X8

Related

ENSP00000490127.1, ENST00000637309.1
XM_017004888.3 → XP_016860377.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X11

UniProtKB/TrEMBL

A0A1B0GWG5
XM_047445796.1 → XP_047301752.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X9
XM_047445793.1 → XP_047301749.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X6

UniProtKB/TrEMBL

A0A1B0GUI8

Related

ENSP00000490430.1, ENST00000635904.1

RNA

XR_007081584.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060926.1 Alternate T2T-CHM13v2.0

Range

152284205..152568400 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054343822.1 → XP_054199797.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X13

UniProtKB/Swiss-Prot

A7BJ74, A8K1Y4, B4DG40, O00305, O60515, Q6B000, Q96L40

UniProtKB/TrEMBL

A8K5R3
XM_054343823.1 → XP_054199798.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X1

UniProtKB/TrEMBL

A0A1B0GTX2, H0Y476
XM_054343825.1 → XP_054199800.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X4

UniProtKB/TrEMBL

A0A1B0GTP5
XM_054343824.1 → XP_054199799.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X2

UniProtKB/TrEMBL

A0A1B0GTX2
XM_054343826.1 → XP_054199801.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X5

UniProtKB/TrEMBL

Q580I4
XM_054343828.1 → XP_054199803.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X12

UniProtKB/TrEMBL

A0A1B0GUU8
XM_054343827.1 → XP_054199802.1 voltage-dependent L-type calcium channel subunit beta-4 isoform X11

UniProtKB/TrEMBL

A0A1B0GWG5