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Protein

Calsequestrin-2

Gene

CASQ2

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

Functioni

Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. Calcium ions are bound by clusters of acidic residues at the protein surface, especially at the interface between subunits. Can bind around 60 Ca2+ ions. Regulates the release of lumenal Ca2+ via the calcium release channel RYR2; this plays an important role in triggering muscle contraction. Plays a role in excitation-contraction coupling in the heart and in regulating the rate of heart beats.4 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionMuscle protein
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels
R-HSA-5578775 Ion homeostasis
SIGNORiO14958

Names & Taxonomyi

Protein namesi
Recommended name:
Calsequestrin-2
Alternative name(s):
Calsequestrin, cardiac muscle isoform
Gene namesi
Name:CASQ2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000118729.11
HGNCiHGNC:1513 CASQ2
MIMi114251 gene
neXtProtiNX_O14958

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

Keywords - Cellular componenti

Sarcoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Ventricular tachycardia, catecholaminergic polymorphic, 2 (CPVT2)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, seizures, or sudden death after physical activity or emotional stress. CPVT2 inheritance is autosomal recessive.
See also OMIM:611938
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05523433R → Q in CPVT2; reduces calcium-dependent dimerization. 2 PublicationsCorresponds to variant dbSNP:rs749547712Ensembl.1
Natural variantiVAR_044118167L → H in CPVT2; alters protein folding; reduces calcium-binding; reduces calcium-dependent oligomerization; decreases sarcoplasmic reticulum Ca(2+) storing capacity; reduces the amplitude of I(Ca)-induced Ca(2+) transients; reduces spontaneous Ca(2+) sparks in permeabilized myocytes. 3 PublicationsCorresponds to variant dbSNP:rs121434550EnsemblClinVar.1
Natural variantiVAR_076546180K → R in CPVT2. 1 PublicationCorresponds to variant dbSNP:rs886039816EnsemblClinVar.1
Natural variantiVAR_016075307D → H in CPVT2; reduces calcium-binding; impairs calcium-dependent oligomerization; causes 50% decrease in calcium-dependent binding to TRDN; causes 50% decrease in calcium-dependent binding to ASPH. 3 PublicationsCorresponds to variant dbSNP:rs121434549EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi845
GeneReviewsiCASQ2
MalaCardsiCASQ2
MIMi611938 phenotype
OpenTargetsiENSG00000118729
Orphaneti3286 Catecholaminergic polymorphic ventricular tachycardia
PharmGKBiPA26096

Polymorphism and mutation databases

BioMutaiCASQ2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19By similarityAdd BLAST19
ChainiPRO_000000421820 – 399Calsequestrin-2Add BLAST380

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei282PhosphotyrosineBy similarity1
Glycosylationi335N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei385Phosphoserine1 Publication1
Modified residuei393Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylation in the C-terminus, probably by CK2, moderately increases calcium buffering capacity.1 Publication
N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO14958
PeptideAtlasiO14958
PRIDEiO14958
ProteomicsDBi48335

PTM databases

iPTMnetiO14958
PhosphoSitePlusiO14958

Expressioni

Gene expression databases

BgeeiENSG00000118729 Expressed in 164 organ(s), highest expression level in myocardium
CleanExiHS_CASQ2
GenevisibleiO14958 HS

Organism-specific databases

HPAiHPA027285
HPA055298

Interactioni

Subunit structurei

Monomer, homodimer and homooligomer. Mostly monomeric in the absence of calcium. Forms higher oligomers in a calcium-dependent manner. Dimers associate to form tetramers, that then form linear homopolymer chains. Interacts with ASPH and TRDN.3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107295, 46 interactors
STRINGi9606.ENSP00000261448

Structurei

3D structure databases

ProteinModelPortaliO14958
SMRiO14958
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14958

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi356 – 399Asp/Glu-rich (acidic)Add BLAST44

Sequence similaritiesi

Belongs to the calsequestrin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IGY5 Eukaryota
ENOG4111R2M LUCA
GeneTreeiENSGT00390000019377
HOGENOMiHOG000049047
HOVERGENiHBG050805
InParanoidiO14958
OMAiTEKNFKQ
OrthoDBiEOG091G08VX
PhylomeDBiO14958
TreeFamiTF313796

Family and domain databases

InterProiView protein in InterPro
IPR001393 Calsequestrin
IPR018233 Calsequestrin_CS
IPR036249 Thioredoxin-like_sf
PANTHERiPTHR10033 PTHR10033, 1 hit
PfamiView protein in Pfam
PF01216 Calsequestrin, 1 hit
SUPFAMiSSF52833 SSF52833, 3 hits
PROSITEiView protein in PROSITE
PS00863 CALSEQUESTRIN_1, 1 hit
PS00864 CALSEQUESTRIN_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: O14958-1) [UniParc]FASTAAdd to basket

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
MKRTHLFIVG IYFLSSCRAE EGLNFPTYDG KDRVVSLSEK NFKQVLKKYD
60 70 80 90 100
LLCLYYHEPV SSDKVTQKQF QLKEIVLELV AQVLEHKAIG FVMVDAKKEA
110 120 130 140 150
KLAKKLGFDE EGSLYILKGD RTIEFDGEFA ADVLVEFLLD LIEDPVEIIS
160 170 180 190 200
SKLEVQAFER IEDYIKLIGF FKSEDSEYYK AFEEAAEHFQ PYIKFFATFD
210 220 230 240 250
KGVAKKLSLK MNEVDFYEPF MDEPIAIPNK PYTEEELVEF VKEHQRPTLR
260 270 280 290 300
RLRPEEMFET WEDDLNGIHI VAFAEKSDPD GYEFLEILKQ VARDNTDNPD
310 320 330 340 350
LSILWIDPDD FPLLVAYWEK TFKIDLFRPQ IGVVNVTDAD SVWMEIPDDD
360 370 380 390
DLPTAEELED WIEDVLSGKI NTEDDDEDDD DDDNSDEEDN DDSDDDDDE
Length:399
Mass (Da):46,436
Last modified:September 19, 2002 - v2
Checksum:i7794DC2FF7E4B064
GO
Isoform 2 (identifier: O14958-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     107-178: GFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEIISSKLEVQAFERIEDYIKLIGFFKSEDSEY → D

Note: No experimental confirmation available.
Show »
Length:328
Mass (Da):38,269
Checksum:i42E722133CA1BCB0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti67Q → P in BAA23494 (Ref. 1) Curated1
Sequence conflicti175D → G in BAG35873 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05523433R → Q in CPVT2; reduces calcium-dependent dimerization. 2 PublicationsCorresponds to variant dbSNP:rs749547712Ensembl.1
Natural variantiVAR_02369266T → A No effect on calcium-binding and calcium-dependent dimerization. 2 PublicationsCorresponds to variant dbSNP:rs4074536EnsemblClinVar.1
Natural variantiVAR_02369376V → M Increases dimerization in the absence of calcium. 2 PublicationsCorresponds to variant dbSNP:rs10801999EnsemblClinVar.1
Natural variantiVAR_044118167L → H in CPVT2; alters protein folding; reduces calcium-binding; reduces calcium-dependent oligomerization; decreases sarcoplasmic reticulum Ca(2+) storing capacity; reduces the amplitude of I(Ca)-induced Ca(2+) transients; reduces spontaneous Ca(2+) sparks in permeabilized myocytes. 3 PublicationsCorresponds to variant dbSNP:rs121434550EnsemblClinVar.1
Natural variantiVAR_076546180K → R in CPVT2. 1 PublicationCorresponds to variant dbSNP:rs886039816EnsemblClinVar.1
Natural variantiVAR_067036244H → R. Corresponds to variant dbSNP:rs28730716EnsemblClinVar.1
Natural variantiVAR_016075307D → H in CPVT2; reduces calcium-binding; impairs calcium-dependent oligomerization; causes 50% decrease in calcium-dependent binding to TRDN; causes 50% decrease in calcium-dependent binding to ASPH. 3 PublicationsCorresponds to variant dbSNP:rs121434549EnsemblClinVar.1
Natural variantiVAR_067037335N → K. Corresponds to variant dbSNP:rs28730712Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056477107 – 178GFDEE…EDSEY → D in isoform 2. 1 PublicationAdd BLAST72

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D55655 mRNA Translation: BAA23494.1
AK295502 mRNA Translation: BAG58422.1
AK313041 mRNA Translation: BAG35873.1
AL449264 Genomic DNA No translation available.
AL450389 Genomic DNA No translation available.
CH471122 Genomic DNA Translation: EAW56635.1
BC022288 mRNA Translation: AAH22288.1
CCDSiCCDS884.1 [O14958-1]
RefSeqiNP_001223.2, NM_001232.3 [O14958-1]
UniGeneiHs.57975

Genome annotation databases

EnsembliENST00000261448; ENSP00000261448; ENSG00000118729 [O14958-1]
GeneIDi845
KEGGihsa:845
UCSCiuc001efx.5 human [O14958-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Calsequestrin entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D55655 mRNA Translation: BAA23494.1
AK295502 mRNA Translation: BAG58422.1
AK313041 mRNA Translation: BAG35873.1
AL449264 Genomic DNA No translation available.
AL450389 Genomic DNA No translation available.
CH471122 Genomic DNA Translation: EAW56635.1
BC022288 mRNA Translation: AAH22288.1
CCDSiCCDS884.1 [O14958-1]
RefSeqiNP_001223.2, NM_001232.3 [O14958-1]
UniGeneiHs.57975

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2VAFX-ray3.80A22-399[»]
ProteinModelPortaliO14958
SMRiO14958
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107295, 46 interactors
STRINGi9606.ENSP00000261448

PTM databases

iPTMnetiO14958
PhosphoSitePlusiO14958

Polymorphism and mutation databases

BioMutaiCASQ2

Proteomic databases

PaxDbiO14958
PeptideAtlasiO14958
PRIDEiO14958
ProteomicsDBi48335

Protocols and materials databases

DNASUi845
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261448; ENSP00000261448; ENSG00000118729 [O14958-1]
GeneIDi845
KEGGihsa:845
UCSCiuc001efx.5 human [O14958-1]

Organism-specific databases

CTDi845
DisGeNETi845
EuPathDBiHostDB:ENSG00000118729.11
GeneCardsiCASQ2
GeneReviewsiCASQ2
HGNCiHGNC:1513 CASQ2
HPAiHPA027285
HPA055298
MalaCardsiCASQ2
MIMi114251 gene
611938 phenotype
neXtProtiNX_O14958
OpenTargetsiENSG00000118729
Orphaneti3286 Catecholaminergic polymorphic ventricular tachycardia
PharmGKBiPA26096
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGY5 Eukaryota
ENOG4111R2M LUCA
GeneTreeiENSGT00390000019377
HOGENOMiHOG000049047
HOVERGENiHBG050805
InParanoidiO14958
OMAiTEKNFKQ
OrthoDBiEOG091G08VX
PhylomeDBiO14958
TreeFamiTF313796

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels
R-HSA-5578775 Ion homeostasis
SIGNORiO14958

Miscellaneous databases

ChiTaRSiCASQ2 human
EvolutionaryTraceiO14958
GenomeRNAii845
PROiPR:O14958
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118729 Expressed in 164 organ(s), highest expression level in myocardium
CleanExiHS_CASQ2
GenevisibleiO14958 HS

Family and domain databases

InterProiView protein in InterPro
IPR001393 Calsequestrin
IPR018233 Calsequestrin_CS
IPR036249 Thioredoxin-like_sf
PANTHERiPTHR10033 PTHR10033, 1 hit
PfamiView protein in Pfam
PF01216 Calsequestrin, 1 hit
SUPFAMiSSF52833 SSF52833, 3 hits
PROSITEiView protein in PROSITE
PS00863 CALSEQUESTRIN_1, 1 hit
PS00864 CALSEQUESTRIN_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCASQ2_HUMAN
AccessioniPrimary (citable) accession number: O14958
Secondary accession number(s): B2R7M6
, B4DIB0, Q5T1D2, Q8TBW8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: September 19, 2002
Last modified: November 7, 2018
This is version 167 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 1
    Human chromosome 1: 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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Main funding by: National Institutes of Health

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