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Protein

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

Gene

CACNB4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Biological processi

  • calcium ion transmembrane transport Source: GOC
  • cardiac conduction Source: Reactome
  • chemical synaptic transmission Source: GO_Central
  • membrane depolarization Source: Reactome
  • neuromuscular junction development Source: GO_Central
  • regulation of voltage-gated calcium channel activity Source: UniProtKB
  • transport Source: ProtInc

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-112308. Depolarization of the Presynaptic Terminal Triggers the Opening of Calcium Channels.
R-HSA-419037. NCAM1 interactions.
R-HSA-5576892. Phase 0 - rapid depolarisation.
R-HSA-5576893. Phase 2 - plateau phase.
R-HSA-5576894. Phase 1 - inactivation of fast Na+ channels.

Protein family/group databases

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

HGNCiHGNC:1404. CACNB4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasmic side of plasma membrane Source: UniProtKB
  • cytosol Source: Reactome
  • plasma membrane Source: UniProtKB
  • synapse Source: UniProtKB
  • voltage-gated calcium channel complex Source: UniProtKB

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
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_013669104C → F in EA5; associated with susceptibility to EIG9. 1 PublicationCorresponds to variant dbSNP:rs1805031Ensembl.1
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:rs1805031Ensembl.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.
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 residuei183PhosphoserineBy similarity1
Modified residuei411PhosphothreonineBy similarity1
Modified residuei506Omega-N-methylarginineBy similarity1

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

MaxQBiO00305.
PaxDbiO00305.
PeptideAtlasiO00305.
PRIDEiO00305.

PTM databases

iPTMnetiO00305.
PhosphoSitePlusiO00305.

Expressioni

Tissue specificityi

Expressed predominantly in the cerebellum and kidney.

Gene expression databases

BgeeiENSG00000182389.
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

WithEntry#Exp.IntActNotes
SYT1P215792EBI-714855,EBI-524909

Protein-protein interaction databases

BioGridi107239. 8 interactors.
IntActiO00305. 9 interactors.
MINTiMINT-1418672.
STRINGi9606.ENSP00000438949.

Structurei

Secondary structure

1520
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi51 – 54Combined sources4
Beta strandi57 – 59Combined sources3
Helixi66 – 68Combined sources3
Turni71 – 73Combined sources3
Helixi74 – 88Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1VYVX-ray3.00A/B254-408[»]
2D46NMR-A50-92[»]
ProteinModelPortaliO00305.
SMRiO00305.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00305.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini118 – 153SH3PROSITE-ProRule annotationAdd BLAST36

Sequence similaritiesi

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiKOG3812. Eukaryota.
ENOG410XRDI. LUCA.
GeneTreeiENSGT00390000002740.
HOGENOMiHOG000230979.
HOVERGENiHBG050765.
InParanoidiO00305.
KOiK04865.
OMAiSYQDSYK.
OrthoDBiEOG090B079H.
PhylomeDBiO00305.
TreeFamiTF316195.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiView protein in InterPro
IPR008145. GK/Ca_channel_bsu.
IPR027417. P-loop_NTPase.
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

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

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:rs1805031Ensembl.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

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
1VYVX-ray3.00A/B254-408[»]
2D46NMR-A50-92[»]
ProteinModelPortaliO00305.
SMRiO00305.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107239. 8 interactors.
IntActiO00305. 9 interactors.
MINTiMINT-1418672.
STRINGi9606.ENSP00000438949.

Chemistry databases

ChEMBLiCHEMBL2363032.
DrugBankiDB04855. Dronedarone.
DB00393. Nimodipine.
DB00421. Spironolactone.
DB00661. Verapamil.

Protein family/group databases

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

PTM databases

iPTMnetiO00305.
PhosphoSitePlusiO00305.

Polymorphism and mutation databases

BioMutaiCACNB4.

Proteomic databases

MaxQBiO00305.
PaxDbiO00305.
PeptideAtlasiO00305.
PRIDEiO00305.

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.
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.
OrthoDBiEOG090B079H.
PhylomeDBiO00305.
TreeFamiTF316195.

Enzyme and pathway databases

ReactomeiR-HSA-112308. Depolarization of the Presynaptic Terminal Triggers the Opening of Calcium Channels.
R-HSA-419037. NCAM1 interactions.
R-HSA-5576892. Phase 0 - rapid depolarisation.
R-HSA-5576893. Phase 2 - plateau phase.
R-HSA-5576894. Phase 1 - inactivation of fast Na+ channels.

Miscellaneous databases

ChiTaRSiCACNB4. human.
EvolutionaryTraceiO00305.
GeneWikiiCACNB4.
GenomeRNAii785.
PROiO00305.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182389.
CleanExiHS_CACNB4.
ExpressionAtlasiO00305. baseline and differential.
GenevisibleiO00305. HS.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiView protein in InterPro
IPR008145. GK/Ca_channel_bsu.
IPR027417. P-loop_NTPase.
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: February 15, 2017
This is version 177 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. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.