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    CACNB4 calcium channel, voltage-dependent, beta 4 subunit [ Homo sapiens ]

    Gene ID: 785, updated on 19-May-2012
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    Summary

    Official Symbol
    CACNB4provided by HGNC
    Official Full Name
    calcium channel, voltage-dependent, beta 4 subunitprovided by HGNC
    Primary source
    HGNC:1404
    See related
    Ensembl:ENSG00000182389; HPRD:09057; MIM:601949; Vega:OTTHUMG00000155091
    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) and juvenile myoclonic epilepsy (JME). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
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    Genomic context

    Location :
    2q22-q23
    Sequence :
    Chromosome: 2; NC_000002.11 (152689285..152955593, complement)
    See CACNB4 in Epigenomics, MapViewer

    Chromosome 2 - NC_000002.11Genomic Context describing neighboring genes Neighboring gene nebulin Neighboring gene ADP-ribosylation factor-like 5A Neighboring gene ribosomal protein L30 pseudogene 2 Neighboring gene signal transducing adaptor molecule (SH3 domain and ITAM motif) 2 Neighboring gene formin-like 2 Neighboring gene nuclear distribution gene C homolog (A. nidulans) pseudogene 1

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Haplotype association mapping of acute lung injury in mice implicates activin a receptor, type 1. Leikauf GD, et al. Am J Respir Crit Care Med, 2011 Jun 1. PMID 21297076.
    2. The Ca2+ channel beta4c subunit interacts with heterochromatin protein 1 via a PXVXL binding motif. Xu X, et al. J Biol Chem, 2011 Mar 18. PMID 21220418.
    3. Replication of previous genome-wide association studies of bone mineral density in premenopausal American women. Ichikawa S, et al. J Bone Miner Res, 2010 Aug. PMID 20200978.
    4. Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening. Voss M, et al. BMC Immunol, 2009 Oct 6. PMID 19807924.
    5. A CACNB4 mutation shows that altered Ca(v)2.1 function may be a genetic modifier of severe myoclonic epilepsy in infancy. Ohmori I, et al. Neurobiol Dis, 2008 Dec. PMID 18755274.

    See all (29) citations in PubMed

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. 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.
    2. 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.
    3. 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.
    4. No pathogenic mutation were identified in CACNB4.
      Title: Episodic ataxia: SLC1A3 and CACNB4 do not explain the apparent genetic heterogeneity.
    5. plays a role in neurotransmitter release.
      Title: [Physiological role of presynaptic Ca2+ channel complexes on neurotransmitter release].
    6. Observational study of gene-disease association. (HuGE Navigator)
      Title: Replication of previous genome-wide association studies of bone mineral density in premenopausal American women.
    7. The novel nucleotide substitution T87C (D29D)in CACNB4 was observed in 2 migrainous vertigo patients and was not present in control DNA samples.
      Title: Migrainous vertigo: mutation analysis of the candidate genes CACNA1A, ATP1A2, SCN1A, and CACNB4.
    Submit: New GeneRIF Correction
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    Phenotypes

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

    Review eQTL and phenotype association data in this region using PheGenI

    Epilepsy, generalized idiopathic

    Epilepsy, idiopathic generalized, susceptibility to, 9

    Epilepsy, juvenile myoclonic

    Episodic ataxia, type 5

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    O00305 O00555 CACNA1A    HPRD  PubMed  
    O00305 Q9Y3C7 MED31    HPRD  PubMed  
    O00305 P21246 PTN    HPRD  PubMed  
    O00305 O75628 REM1    HPRD  PubMed  
    O00305 Q12788 TBL3    HPRD  PubMed  
    BioGRID:107239 BioGRID:107227 CACNA1A    BioGRID  PubMed Reconstituted Complex 
    BioGRID:107239 BioGRID:119211 MED31    BioGRID  PubMed Two-hybrid 
    BioGRID:107239 BioGRID:111731 PTN    BioGRID  PubMed Two-hybrid 
    BioGRID:107239 BioGRID:115853 TBL3    BioGRID  PubMed Two-hybrid 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Arrhythmogenic right ventricular cardiomyopathy (ARVC), organism-specific biosystem (from KEGG)
      Arrhythmogenic right ventricular cardiomyopathy (ARVC), organism-specific biosystemArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are prog...
    • Arrhythmogenic right ventricular cardiomyopathy (ARVC), conserved biosystem (from KEGG)
      Arrhythmogenic right ventricular cardiomyopathy (ARVC), conserved biosystemArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are prog...
    • Axon guidance, organism-specific biosystem (from REACTOME)
      Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
    • Cardiac muscle contraction, organism-specific biosystem (from KEGG)
      Cardiac muscle contraction, organism-specific biosystemContraction of the heart is a complex process initiated by the electrical excitation of cardiac myocytes (excitation-contraction coupling, ECC). In cardiac myocytes, Ca2+ influx induced by activation...
    • Cardiac muscle contraction, conserved biosystem (from KEGG)
      Cardiac muscle contraction, conserved biosystemContraction of the heart is a complex process initiated by the electrical excitation of cardiac myocytes (excitation-contraction coupling, ECC). In cardiac myocytes, Ca2+ influx induced by activation...
    • Depolarization of the Presynaptic Terminal Triggers the Opening of Calcium Channels, organism-specific biosystem (from REACTOME)
      Depolarization of the Presynaptic Terminal Triggers the Opening of Calcium Channels, organism-specific biosystemThe action potential travels down the axon and reaches the pre-synaptic terminal depolarizing the membrane in the pre-synaptic terminal. The depolarization causes the voltage-gated Ca2+ channels to ...
    • Developmental Biology, organism-specific biosystem (from REACTOME)
      Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
    • Dilated cardiomyopathy, organism-specific biosystem (from KEGG)
      Dilated cardiomyopathy, organism-specific biosystemDilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac d...
    • Dilated cardiomyopathy, conserved biosystem (from KEGG)
      Dilated cardiomyopathy, conserved biosystemDilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac d...
    • Hypertrophic cardiomyopathy (HCM), organism-specific biosystem (from KEGG)
      Hypertrophic cardiomyopathy (HCM), organism-specific biosystemHypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological feat...
    • Hypertrophic cardiomyopathy (HCM), conserved biosystem (from KEGG)
      Hypertrophic cardiomyopathy (HCM), conserved biosystemHypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological feat...
    • MAPK signaling pathway, organism-specific biosystem (from KEGG)
      MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MAPK signaling pathway, conserved biosystem (from KEGG)
      MAPK signaling pathway, conserved biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • NCAM signaling for neurite out-growth, organism-specific biosystem (from REACTOME)
      NCAM signaling for neurite out-growth, organism-specific biosystemThe neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the n...
    • NCAM1 interactions, organism-specific biosystem (from REACTOME)
      NCAM1 interactions, organism-specific biosystemThe neural cell adhesion molecule, NCAM1 is generally considered as a cell adhesion mediator, but it is also considered to be a signal transducing receptor molecule. NCAM1 is involved in multiple cis...
    • Neuronal System, organism-specific biosystem (from REACTOME)
      Neuronal System, organism-specific biosystemThe human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication a...
    • Transmission across Chemical Synapses, organism-specific biosystem (from REACTOME)
      Transmission across Chemical Synapses, organism-specific biosystemChemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron,...

    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 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    contributes_to voltage-gated calcium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    voltage-gated ion channel activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    axon guidance TAS
    Traceable Author Statement
    more info
    		  
    ion transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    membrane depolarization TAS
    Traceable Author Statement
    more info
    		  
    regulation of calcium ion transport via voltage-gated calcium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    synaptic transmission TAS
    Traceable Author Statement
    more info
    		  
    transport TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    internal side of plasma membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    synapse IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    voltage-gated calcium channel complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    voltage-dependent L-type calcium channel subunit beta-4
    Names
    voltage-dependent L-type calcium channel subunit beta-4
    calcium channel voltage-dependent subunit beta 4
    dihydropyridine-sensitive L-type, calcium channel beta-4 subunit
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    NCBI Reference Sequences (RefSeq)

    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

    1. NG_012641.1 RefSeqGene

      Range
      5001..271309
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000726.3 → NP_000717.2  voltage-dependent L-type calcium channel subunit beta-4 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) encodes the longest isoform (b).
      Source sequence(s)
      AC097448, BC075049, T23939, U95020
      Consensus CDS
      CCDS46426.1
      UniProtKB/Swiss-Prot
      O00305
      Related
      ENSP00000438949, OTTHUMP00000207249, ENST00000539935, OTTHUMT00000338385
      Conserved Domains (4) summary
      pfam00625
      Location:218 – 398
      Blast Score: 444
      Guanylate_kin; Guanylate kinase
      pfam12052
      Location:50 – 91
      Blast Score: 176
      VGCC_beta4Aa_N; Voltage gated calcium channel subunit beta domain 4Aa N terminal
      cl15350
      Location:118 – 153
      Blast Score: 102
      SH3; Src homology 3 domains; SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of ...
      cl09099
      Location:228 – 399
      Blast Score: 268
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    2. NM_001005746.2 → NP_001005746.1  voltage-dependent L-type calcium channel subunit beta-4 isoform c

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents use of an alternate promoter and 5' UTR and differs in the 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)
      AC097448, AK316045, BX279713, T23939
      Consensus CDS
      CCDS46427.1
      Related
      ENSP00000410978, OTTHUMP00000207247, ENST00000427385, OTTHUMT00000338428
      Conserved Domains (4) summary
      pfam00625
      Location:200 – 380
      Blast Score: 443
      Guanylate_kin; Guanylate kinase
      pfam12052
      Location:32 – 73
      Blast Score: 177
      VGCC_beta4Aa_N; Voltage gated calcium channel subunit beta domain 4Aa N terminal
      cl15350
      Location:100 – 135
      Blast Score: 102
      SH3; Src homology 3 domains; SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of ...
      cl09099
      Location:210 – 381
      Blast Score: 267
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    3. NM_001005747.2 → NP_001005747.1  voltage-dependent L-type calcium channel subunit beta-4 isoform a

      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.
      Source sequence(s)
      AC097448, AK290049, DA782833, T23939
      Consensus CDS
      CCDS46428.1
      UniProtKB/Swiss-Prot
      O00305
      Related
      ENSP00000443893, OTTHUMP00000207228, ENST00000534999, OTTHUMT00000338383
      Conserved Domains (4) summary
      pfam00625
      Location:184 – 364
      Blast Score: 442
      Guanylate_kin; Guanylate kinase
      pfam12052
      Location:16 – 57
      Blast Score: 180
      VGCC_beta4Aa_N; Voltage gated calcium channel subunit beta domain 4Aa N terminal
      cl15350
      Location:84 – 119
      Blast Score: 101
      SH3; Src homology 3 domains; SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of ...
      cl09099
      Location:194 – 365
      Blast Score: 267
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    4. NM_001145798.1 → NP_001139270.1  voltage-dependent L-type calcium channel subunit beta-4 isoform d

      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.
      Source sequence(s)
      AB302276, AC097448, T23939, U95020
      Consensus CDS
      CCDS54409.1
      UniProtKB/Swiss-Prot
      O00305
      Related
      ENSP00000201943, OTTHUMP00000207246, ENST00000201943, OTTHUMT00000338427
      Conserved Domains (3) summary
      pfam12052
      Location:50 – 91
      Blast Score: 173
      VGCC_beta4Aa_N; Voltage gated calcium channel subunit beta domain 4Aa N terminal
      cl15350
      Location:118 – 153
      Blast Score: 102
      SH3; Src homology 3 domains; SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of ...
      cl09099
      Location:228 – 372
      Blast Score: 204
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000002.11 Reference GRCh37.p5 Primary Assembly

      Range
      152689285..152955593, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000134.1 Alternate HuRef

      Range
      144575492..144841767, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC068547.7 AAY14759.1
    genomic AC079790.6 AAY14711.1
    genomic AC097448.2 AAX82014.1
    genomic AF216867.1 AAF61674.1
    genomic CH471058.2 EAX11493.1
      EAX11494.1
    mRNA AB302276.1 BAF73808.1
    mRNA AF038852.1 AAC24206.1
    mRNA AF075047.1 None
    mRNA AK290049.1 BAF82738.1
    mRNA AK291378.1 BAF84067.1
    mRNA AK294398.1 BAG57651.1
    mRNA AK316045.1 BAH14416.1
    mRNA AL700210.1 None
    mRNA AY054985.1 AAL14351.1
    mRNA BC075049.2 AAH75049.1
    mRNA BP229182.1 None
    mRNA BP360802.1 None
    mRNA BX279713.1 None
    mRNA BX484858.1 None
    mRNA BX648679.1 None
    mRNA DA782833.1 None
    mRNA HQ214056.1 ADP09414.1
    mRNA T23939.1 None
    mRNA U95020.1 AAB53333.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    O00305.2 GenPept UniProtKB/Swiss-Prot:O00305
    Q53S65 GenPept UniProtKB/TrEMBL:Q53S65
    Q580I4 GenPept UniProtKB/TrEMBL:Q580I4
    Q9NZA2 GenPept UniProtKB/TrEMBL:Q9NZA2
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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