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Protein

Voltage-dependent L-type calcium channel subunit beta-4

Gene

CACNB4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.1 Publication

GO - Molecular functioni

  • calcium channel activity Source: Reactome
  • high voltage-gated calcium channel activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionCalcium channel, Ion channel, Voltage-gated channel
Biological processCalcium transport, Ion transport, Transport
LigandCalcium

Enzyme and pathway databases

ReactomeiR-HSA-112308 Presynaptic depolarization and calcium channel opening
R-HSA-419037 NCAM1 interactions
R-HSA-5576892 Phase 0 - rapid depolarisation
R-HSA-5576893 Phase 2 - plateau phase

Protein family/group databases

TCDBi8.A.22.1.4 the ca(2+) channel auxiliary subunit Beta types 1-4 (cca-Beta) family

Names & Taxonomyi

Protein namesi
Recommended name:
Voltage-dependent L-type calcium channel subunit beta-4Curated
Short name:
CAB4Curated
Alternative name(s):
Calcium channel voltage-dependent subunit beta 4Curated
Gene namesi
Name:CACNB4Imported
Synonyms:CACNLB4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000182389.18
HGNCiHGNC:1404 CACNB4
MIMi601949 gene
neXtProtiNX_O00305

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Epilepsy, idiopathic generalized 9 (EIG9)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain.
See also OMIM:607682
Juvenile myoclonic epilepsy 6 (EJM6)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue.
See also OMIM:607682
Episodic ataxia 5 (EA5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by episodes of vertigo and ataxia that last for several hours. Interictal examination show spontaneous downbeat and gaze-evoked nystagmus, mild dysarthria and truncal ataxia.
See also OMIM:613855
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_013669104C → F in EA5; associated with susceptibility to EIG9. 1 PublicationCorresponds to variant dbSNP:rs1805031EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi785
MalaCardsiCACNB4
MIMi607682 phenotype
613855 phenotype
OpenTargetsiENSG00000182389
Orphaneti211067 Episodic ataxia type 5
307 Juvenile myoclonic epilepsy
PharmGKBiPA26014

Chemistry databases

ChEMBLiCHEMBL2363032
DrugBankiDB04855 Dronedarone
DB01388 Mibefradil
DB00393 Nimodipine
DB00421 Spironolactone
DB00661 Verapamil

Polymorphism and mutation databases

BioMutaiCACNB4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001440601 – 520Voltage-dependent L-type calcium channel subunit beta-4Add BLAST520

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei39PhosphoserineBy similarity1
Modified residuei183PhosphoserineBy similarity1
Modified residuei411PhosphothreonineBy similarity1
Modified residuei448PhosphoserineBy similarity1
Modified residuei506Omega-N-methylarginineBy similarity1
Modified residuei508PhosphoserineBy similarity1

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

MaxQBiO00305
PaxDbiO00305
PeptideAtlasiO00305
PRIDEiO00305
ProteomicsDBi47831
47832 [O00305-2]
47833 [O00305-3]
47834 [O00305-4]

PTM databases

iPTMnetiO00305
PhosphoSitePlusiO00305

Expressioni

Tissue specificityi

Expressed predominantly in the cerebellum and kidney.

Gene expression databases

BgeeiENSG00000182389 Expressed in 140 organ(s), highest expression level in caudate nucleus
CleanExiHS_CACNB4
ExpressionAtlasiO00305 baseline and differential
GenevisibleiO00305 HS

Organism-specific databases

HPAiHPA015601

Interactioni

Subunit structurei

The L-type calcium channel is composed of four subunits: alpha-1, alpha-2, beta and gamma (PubMed:11880487). Interacts with FASLG (PubMed:19807924). Interacts with CBARP (By similarity).By similarity2 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi107239, 8 interactors
IntActiO00305, 10 interactors
STRINGi9606.ENSP00000438949

Structurei

Secondary structure

1520
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO00305
SMRiO00305
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00305

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini92 – 161SH3PROSITE-ProRule annotationAdd BLAST70

Sequence similaritiesi

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiKOG3812 Eukaryota
ENOG410XRDI LUCA
GeneTreeiENSGT00390000002740
HOGENOMiHOG000230979
HOVERGENiHBG050765
InParanoidiO00305
KOiK04865
OMAiSYQDSYK
OrthoDBiEOG091G09C1
PhylomeDBiO00305
TreeFamiTF316195

Family and domain databases

InterProiView protein in InterPro
IPR008145 GK/Ca_channel_bsu
IPR027417 P-loop_NTPase
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR000584 VDCC_L_bsu
PANTHERiPTHR11824 PTHR11824, 1 hit
PfamiView protein in Pfam
PF00625 Guanylate_kin, 1 hit
PF12052 VGCC_beta4Aa_N, 1 hit
PRINTSiPR01626 LCACHANNELB
SMARTiView protein in SMART
SM00072 GuKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS50002 SH3, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 46 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O00305-1) [UniParc]FASTAAdd to basket
Also known as: 4b

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSSSSYAKNG TADGPHSPTS QVARGTTTRR SRLKRSDGST TSTSFILRQG
60 70 80 90 100
SADSYTSRPS DSDVSLEEDR EAIRQEREQQ AAIQLERAKS KPVAFAVKTN
110 120 130 140 150
VSYCGALDED VPVPSTAISF DAKDFLHIKE KYNNDWWIGR LVKEGCEIGF
160 170 180 190 200
IPSPLRLENI RIQQEQKRGR FHGGKSSGNS SSSLGEMVSG TFRATPTSTA
210 220 230 240 250
KQKQKVTEHI PPYDVVPSMR PVVLVGPSLK GYEVTDMMQK ALFDFLKHRF
260 270 280 290 300
DGRISITRVT ADISLAKRSV LNNPSKRAII ERSNTRSSLA EVQSEIERIF
310 320 330 340 350
ELARSLQLVV LDADTINHPA QLIKTSLAPI IVHVKVSSPK VLQRLIKSRG
360 370 380 390 400
KSQSKHLNVQ LVAADKLAQC PPEMFDVILD ENQLEDACEH LGEYLEAYWR
410 420 430 440 450
ATHTTSSTPM TPLLGRNLGS TALSPYPTAI SGLQSQRMRH SNHSTENSPI
460 470 480 490 500
ERRSLMTSDE NYHNERARKS RNRLSSSSQH SRDHYPLVEE DYPDSYQDTY
510 520
KPHRNRGSPG GYSHDSRHRL
Length:520
Mass (Da):58,169
Last modified:February 6, 2007 - v2
Checksum:i21025FA9782347FA
GO
Isoform 2 (identifier: O00305-2) [UniParc]FASTAAdd to basket
Also known as: 4a

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: MSSSSYAKNGTADGPHSPTSQVARGTTTRRSRLKRSDGSTTSTSFILRQ → MYDNLYLHGIEDSEA

Show »
Length:486
Mass (Da):54,707
Checksum:i5E8F03EA98A88597
GO
Isoform 3 (identifier: O00305-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: MSSSSYAKNGTADGPHSPTSQ → MDV

Note: No experimental confirmation available.
Show »
Length:502
Mass (Da):56,422
Checksum:i24BA6BA3A89A46BB
GO
Isoform 4 (identifier: O00305-4) [UniParc]FASTAAdd to basket
Also known as: 4d

The sequence of this isoform differs from the canonical sequence as follows:
     373-434: Missing.

Note: Unable to interact with the alpha-1 subunit.
Show »
Length:458
Mass (Da):51,331
Checksum:i4AC560044A3BA110
GO

Computationally mapped potential isoform sequencesi

There are 46 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y476H0Y476_HUMAN
Voltage-dependent L-type calcium ch...
CACNB4
473Annotation score:
E7DBM8E7DBM8_HUMAN
Voltage-dependent L-type calcium ch...
CACNB4
207Annotation score:
E7EN11E7EN11_HUMAN
Voltage-dependent L-type calcium ch...
CACNB4
441Annotation score:
A0A1B0GTK1A0A1B0GTK1_HUMAN
Voltage-dependent L-type calcium ch...
CACNB4
423Annotation score:
A0A1B0GTX8A0A1B0GTX8_HUMAN
Voltage-dependent L-type calcium ch...
CACNB4
410Annotation score:
C9J224C9J224_HUMAN
Voltage-dependent L-type calcium ch...
CACNB4
125Annotation score:
A0A1B0GXG0A0A1B0GXG0_HUMAN
Voltage-dependent L-type calcium ch...
CACNB4
472Annotation score:
A0A1B0GUW8A0A1B0GUW8_HUMAN
Voltage-dependent L-type calcium ch...
CACNB4
215Annotation score:
A0A1B0GU53A0A1B0GU53_HUMAN
Voltage-dependent L-type calcium ch...
CACNB4
424Annotation score:
A0A1B0GTS4A0A1B0GTS4_HUMAN
Voltage-dependent L-type calcium ch...
CACNB4
411Annotation score:
There are more potential isoformsShow all

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti245F → S in AAB53333 (PubMed:9254841).Curated1
Sequence conflicti245F → S in AAL14351 (PubMed:11880487).Curated1
Sequence conflicti311L → V in AAL14351 (PubMed:11880487).Curated1
Sequence conflicti441S → T in AAL14351 (PubMed:11880487).Curated1
Isoform 2 (identifier: O00305-2)
Sequence conflicti12D → N in AAL14351 (PubMed:11880487).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_013669104C → F in EA5; associated with susceptibility to EIG9. 1 PublicationCorresponds to variant dbSNP:rs1805031EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0006351 – 49MSSSS…FILRQ → MYDNLYLHGIEDSEA in isoform 2. 2 PublicationsAdd BLAST49
Alternative sequenceiVSP_0431921 – 21MSSSS…SPTSQ → MDV in isoform 3. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_043193373 – 434Missing in isoform 4. 1 PublicationAdd BLAST62

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U95020 mRNA Translation: AAB53333.1
AY054985 mRNA Translation: AAL14351.1
AB302276 mRNA Translation: BAF73808.1
AK290049 mRNA Translation: BAF82738.1
AK294398 mRNA Translation: BAG57651.1
AK316045 mRNA Translation: BAH14416.1
AC068547 Genomic DNA No translation available.
AC079790 Genomic DNA No translation available.
AC097448 Genomic DNA No translation available.
CH471058 Genomic DNA Translation: EAX11494.1
BC075049 mRNA Translation: AAH75049.1
AF038852 mRNA Translation: AAC24206.1
CCDSiCCDS46426.1 [O00305-1]
CCDS46427.1 [O00305-3]
CCDS46428.1 [O00305-2]
CCDS54409.1 [O00305-4]
RefSeqiNP_000717.2, NM_000726.4 [O00305-1]
NP_001005746.1, NM_001005746.3 [O00305-3]
NP_001005747.1, NM_001005747.3 [O00305-2]
NP_001139270.1, NM_001145798.2 [O00305-4]
NP_001307651.1, NM_001320722.2
UniGeneiHs.120725

Genome annotation databases

EnsembliENST00000201943; ENSP00000201943; ENSG00000182389 [O00305-4]
ENST00000534999; ENSP00000443893; ENSG00000182389 [O00305-2]
ENST00000539935; ENSP00000438949; ENSG00000182389 [O00305-1]
ENST00000638005; ENSP00000489677; ENSG00000182389 [O00305-3]
GeneIDi785
KEGGihsa:785
UCSCiuc002txy.5 human [O00305-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U95020 mRNA Translation: AAB53333.1
AY054985 mRNA Translation: AAL14351.1
AB302276 mRNA Translation: BAF73808.1
AK290049 mRNA Translation: BAF82738.1
AK294398 mRNA Translation: BAG57651.1
AK316045 mRNA Translation: BAH14416.1
AC068547 Genomic DNA No translation available.
AC079790 Genomic DNA No translation available.
AC097448 Genomic DNA No translation available.
CH471058 Genomic DNA Translation: EAX11494.1
BC075049 mRNA Translation: AAH75049.1
AF038852 mRNA Translation: AAC24206.1
CCDSiCCDS46426.1 [O00305-1]
CCDS46427.1 [O00305-3]
CCDS46428.1 [O00305-2]
CCDS54409.1 [O00305-4]
RefSeqiNP_000717.2, NM_000726.4 [O00305-1]
NP_001005746.1, NM_001005746.3 [O00305-3]
NP_001005747.1, NM_001005747.3 [O00305-2]
NP_001139270.1, NM_001145798.2 [O00305-4]
NP_001307651.1, NM_001320722.2
UniGeneiHs.120725

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D46NMR-A50-92[»]
ProteinModelPortaliO00305
SMRiO00305
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107239, 8 interactors
IntActiO00305, 10 interactors
STRINGi9606.ENSP00000438949

Chemistry databases

ChEMBLiCHEMBL2363032
DrugBankiDB04855 Dronedarone
DB01388 Mibefradil
DB00393 Nimodipine
DB00421 Spironolactone
DB00661 Verapamil

Protein family/group databases

TCDBi8.A.22.1.4 the ca(2+) channel auxiliary subunit Beta types 1-4 (cca-Beta) family

PTM databases

iPTMnetiO00305
PhosphoSitePlusiO00305

Polymorphism and mutation databases

BioMutaiCACNB4

Proteomic databases

MaxQBiO00305
PaxDbiO00305
PeptideAtlasiO00305
PRIDEiO00305
ProteomicsDBi47831
47832 [O00305-2]
47833 [O00305-3]
47834 [O00305-4]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000201943; ENSP00000201943; ENSG00000182389 [O00305-4]
ENST00000534999; ENSP00000443893; ENSG00000182389 [O00305-2]
ENST00000539935; ENSP00000438949; ENSG00000182389 [O00305-1]
ENST00000638005; ENSP00000489677; ENSG00000182389 [O00305-3]
GeneIDi785
KEGGihsa:785
UCSCiuc002txy.5 human [O00305-1]

Organism-specific databases

CTDi785
DisGeNETi785
EuPathDBiHostDB:ENSG00000182389.18
GeneCardsiCACNB4
HGNCiHGNC:1404 CACNB4
HPAiHPA015601
MalaCardsiCACNB4
MIMi601949 gene
607682 phenotype
613855 phenotype
neXtProtiNX_O00305
OpenTargetsiENSG00000182389
Orphaneti211067 Episodic ataxia type 5
307 Juvenile myoclonic epilepsy
PharmGKBiPA26014
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3812 Eukaryota
ENOG410XRDI LUCA
GeneTreeiENSGT00390000002740
HOGENOMiHOG000230979
HOVERGENiHBG050765
InParanoidiO00305
KOiK04865
OMAiSYQDSYK
OrthoDBiEOG091G09C1
PhylomeDBiO00305
TreeFamiTF316195

Enzyme and pathway databases

ReactomeiR-HSA-112308 Presynaptic depolarization and calcium channel opening
R-HSA-419037 NCAM1 interactions
R-HSA-5576892 Phase 0 - rapid depolarisation
R-HSA-5576893 Phase 2 - plateau phase

Miscellaneous databases

ChiTaRSiCACNB4 human
EvolutionaryTraceiO00305
GeneWikiiCACNB4
GenomeRNAii785
PROiPR:O00305
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182389 Expressed in 140 organ(s), highest expression level in caudate nucleus
CleanExiHS_CACNB4
ExpressionAtlasiO00305 baseline and differential
GenevisibleiO00305 HS

Family and domain databases

InterProiView protein in InterPro
IPR008145 GK/Ca_channel_bsu
IPR027417 P-loop_NTPase
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR000584 VDCC_L_bsu
PANTHERiPTHR11824 PTHR11824, 1 hit
PfamiView protein in Pfam
PF00625 Guanylate_kin, 1 hit
PF12052 VGCC_beta4Aa_N, 1 hit
PRINTSiPR01626 LCACHANNELB
SMARTiView protein in SMART
SM00072 GuKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS50002 SH3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCACB4_HUMAN
AccessioniPrimary (citable) accession number: O00305
Secondary accession number(s): A7BJ74
, A8K1Y4, B4DG40, O60515, Q6B000, Q96L40
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: February 6, 2007
Last modified: November 7, 2018
This is version 191 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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