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Protein

Calsequestrin-2

Gene

CASQ2

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

  • calcium-dependent protein binding Source: UniProtKB
  • calcium ion binding Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL

GO - Biological processi

  • cardiac muscle contraction Source: BHF-UCL
  • cellular response to caffeine Source: BHF-UCL
  • detection of calcium ion Source: BHF-UCL
  • ion transmembrane transport Source: Reactome
  • negative regulation of potassium ion transmembrane transporter activity Source: BHF-UCL
  • negative regulation of potassium ion transport Source: BHF-UCL
  • negative regulation of ryanodine-sensitive calcium-release channel activity Source: BHF-UCL
  • protein polymerization Source: UniProtKB
  • Purkinje myocyte to ventricular cardiac muscle cell signaling Source: BHF-UCL
  • regulation of cardiac conduction Source: Reactome
  • regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: BHF-UCL
  • regulation of cell communication by electrical coupling Source: BHF-UCL
  • regulation of heart rate Source: UniProtKB
  • regulation of membrane repolarization Source: BHF-UCL
  • regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: BHF-UCL
  • sarcomere organization Source: Ensembl
  • sequestering of calcium ion Source: BHF-UCL
  • striated muscle contraction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Muscle protein

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000118729-MONOMER.
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

HGNCiHGNC:1513. CASQ2.

Subcellular locationi

  • Sarcoplasmic reticulum lumen By similarity

  • Note: This isoform of calsequestrin occurs in the sarcoplasmic reticulum's terminal cisternae luminal spaces of cardiac and slow skeletal muscle cells.By similarity

GO - Cellular componenti

  • calcium channel complex Source: BHF-UCL
  • cytoplasm Source: BHF-UCL
  • intracellular Source: BHF-UCL
  • junctional membrane complex Source: Ensembl
  • junctional sarcoplasmic reticulum membrane Source: BHF-UCL
  • sarcoplasmic reticulum Source: BHF-UCL
  • sarcoplasmic reticulum lumen Source: BHF-UCL
  • sarcoplasmic reticulum membrane Source: Reactome
  • Z disc Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Sarcoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Ventricular tachycardia, catecholaminergic polymorphic, 2 (CPVT2)4 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.
See also OMIM:611938
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05523433R → Q in CPVT2; reduces calcium-dependent dimerization. 2 PublicationsCorresponds to variant rs749547712dbSNPEnsembl.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 rs121434550dbSNPEnsembl.1
Natural variantiVAR_076546180K → R in CPVT2. 1 Publication1
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 rs121434549dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi845.
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...)Sequence 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.

PTM databases

iPTMnetiO14958.
PhosphoSitePlusiO14958.

Expressioni

Gene expression databases

BgeeiENSG00000118729.
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

  • calcium-dependent protein binding Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi107295. 44 interactors.
STRINGi9606.ENSP00000261448.

Structurei

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...

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.
OMAiAIPNKPY.
OrthoDBiEOG091G08VX.
PhylomeDBiO14958.
TreeFamiTF313796.

Family and domain databases

Gene3Di3.40.30.10. 3 hits.
InterProiIPR001393. Calsequestrin.
IPR018233. Calsequestrin_CS.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PfamiPF01216. Calsequestrin. 1 hit.
[Graphical view]
PRINTSiPR00312. CALSEQUESTRN.
SUPFAMiSSF52833. SSF52833. 3 hits.
PROSITEiPS00863. CALSEQUESTRIN_1. 1 hit.
PS00864. CALSEQUESTRIN_2. 1 hit.
[Graphical view]

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 rs749547712dbSNPEnsembl.1
Natural variantiVAR_02369266T → A No effect on calcium-binding and calcium-dependent dimerization. 2 PublicationsCorresponds to variant rs4074536dbSNPEnsembl.1
Natural variantiVAR_02369376V → M Increases dimerization in the absence of calcium. 2 PublicationsCorresponds to variant rs10801999dbSNPEnsembl.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 rs121434550dbSNPEnsembl.1
Natural variantiVAR_076546180K → R in CPVT2. 1 Publication1
Natural variantiVAR_067036244H → R.Corresponds to variant rs28730716dbSNPEnsembl.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 rs121434549dbSNPEnsembl.1
Natural variantiVAR_067037335N → K.Corresponds to variant rs28730712dbSNPEnsembl.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, AL450389 Genomic DNA. Translation: CAI14532.1.
AL450389, AL449264 Genomic DNA. Translation: CAI23373.1.
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

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, AL450389 Genomic DNA. Translation: CAI14532.1.
AL450389, AL449264 Genomic DNA. Translation: CAI23373.1.
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. 44 interactors.
STRINGi9606.ENSP00000261448.

PTM databases

iPTMnetiO14958.
PhosphoSitePlusiO14958.

Polymorphism and mutation databases

BioMutaiCASQ2.

Proteomic databases

PaxDbiO14958.
PeptideAtlasiO14958.
PRIDEiO14958.

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.
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.
OMAiAIPNKPY.
OrthoDBiEOG091G08VX.
PhylomeDBiO14958.
TreeFamiTF313796.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000118729-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.
R-HSA-5578775. Ion homeostasis.
SIGNORiO14958.

Miscellaneous databases

ChiTaRSiCASQ2. human.
EvolutionaryTraceiO14958.
GenomeRNAii845.
PROiO14958.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118729.
CleanExiHS_CASQ2.
GenevisibleiO14958. HS.

Family and domain databases

Gene3Di3.40.30.10. 3 hits.
InterProiIPR001393. Calsequestrin.
IPR018233. Calsequestrin_CS.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PfamiPF01216. Calsequestrin. 1 hit.
[Graphical view]
PRINTSiPR00312. CALSEQUESTRN.
SUPFAMiSSF52833. SSF52833. 3 hits.
PROSITEiPS00863. CALSEQUESTRIN_1. 1 hit.
PS00864. CALSEQUESTRIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCASQ2_HUMAN
AccessioniPrimary (citable) accession number: O14958
Secondary accession number(s): B2R7M6
, B4DIB0, Q5T1D2, Q8TBW8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: September 19, 2002
Last modified: November 2, 2016
This is version 154 of the entry and version 2 of the sequence. [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 1
    Human chromosome 1: 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.