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Protein

Calsequestrin-2

Gene

Casq2

Organism
Mus musculus (Mouse)
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.3 Publications

GO - Molecular functioni

  • calcium-dependent protein binding Source: MGI
  • calcium ion binding Source: UniProtKB

GO - Biological processi

  • cardiac muscle contraction Source: MGI
  • cellular response to caffeine Source: MGI
  • 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: MGI
  • protein polymerization Source: MGI
  • regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: MGI
  • regulation of cell communication by electrical coupling Source: MGI
  • regulation of heart rate Source: UniProtKB
  • regulation of membrane repolarization Source: BHF-UCL
  • regulation of muscle contraction Source: MGI
  • regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: UniProtKB
  • sarcomere organization Source: UniProtKB
  • sequestering of calcium ion Source: MGI

Keywordsi

Molecular functionMuscle protein
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-2672351 Stimuli-sensing channels
R-MMU-5578775 Ion homeostasis

Names & Taxonomyi

Protein namesi
Recommended name:
Calsequestrin-2
Alternative name(s):
Calsequestrin, cardiac muscle isoform
Gene namesi
Name:Casq2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1309469 Casq2

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

Disruption phenotypei

Mutant mice are born at the expected Mendelian rate, are viable and display normal sarcoplasmic calcium release and normal heart function under basal conditions, but have a slower heart rate. Mutant mice are subject to polymorphic arrhythmia after exercise and to catecholaminergic ventricular arrhythmia, and their myocytes show increased Ca2+ release in response to isoproterenol. Besides, the volume of the junctional sarcoplasmic reticulum is increased, and it seems to lack visible content.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi307D → H: Impairs calcium-dependent oligomerization and promotes ventricular tachycardia. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000000421920 – 415Calsequestrin-2Add BLAST396

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei282PhosphotyrosineCombined sources1
Glycosylationi335N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Phosphorylation in the C-terminus moderately increases calcium buffering capacity.By similarity
N-glycosylated.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiO09161
PaxDbiO09161
PRIDEiO09161

PTM databases

iPTMnetiO09161
PhosphoSitePlusiO09161

Expressioni

Tissue specificityi

Detected in heart (at protein level). Detected in heart.3 Publications

Gene expression databases

BgeeiENSMUSG00000027861
CleanExiMM_CASQ2
ExpressionAtlasiO09161 baseline and differential
GenevisibleiO09161 MM

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 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiO09161, 1 interactor
MINTiO09161
STRINGi10090.ENSMUSP00000029454

Structurei

3D structure databases

ProteinModelPortaliO09161
SMRiO09161
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi373 – 415Asp/Glu-rich (acidic)Add BLAST43

Sequence similaritiesi

Belongs to the calsequestrin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IGY5 Eukaryota
ENOG4111R2M LUCA
GeneTreeiENSGT00390000019377
HOVERGENiHBG050805
InParanoidiO09161
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

Sequencei

Sequence statusi: Complete.

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

O09161-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKRIYLLMVG VYLLSLSGAE EGLNFPTYDG KDRVVSLSEK NLKQMLKRYD
60 70 80 90 100
LLCLYYHEPV SSDKVSQKQF QLKEIVLELV AQVLEHKNIG FVMVDSRKEA
110 120 130 140 150
KLAKRLGFSE EGSLYVLKGD RTIEFDGEFA ADVLVEFLLD LIEDPVEIVN
160 170 180 190 200
NKLEVQAFER IEDQTKLLGF FKNEDSEYYK AFQEAAEHFQ PYIKFFATFD
210 220 230 240 250
KAVAKKLSLK MNEVGFYEPF MDEPNVIPNK PYTEEELVEF VKEHQRPTLR
260 270 280 290 300
RLRPEDMFET WEDDLNGIHI VAFAEKSDPD GYEFLEILKQ VARDNTDNPD
310 320 330 340 350
LSILWIDPDD FPLLVAYWEK TFKIDLFKPQ IGVVNVTDAD SIWMEIPDDD
360 370 380 390 400
DLPTAEELED WIEDVLSGKI NTEDDDNEDE DDDGDDNDDD DDDDDDNDNS
410
DEDNEDSDDD DDDDE
Length:415
Mass (Da):48,176
Last modified:July 27, 2011 - v3
Checksum:i82D7680878A6E3B5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1 – 2MK → MER in AAC82512 (PubMed:9795116).Curated2
Sequence conflicti20E → Q in AAC82512 (PubMed:9795116).Curated1
Sequence conflicti278D → H in AAC82512 (PubMed:9795116).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U91483 mRNA Translation: AAC82512.1
AF068244 mRNA Translation: AAC69472.1
CH466608 Genomic DNA Translation: EDL07619.1
BC092229 mRNA Translation: AAH92229.1
BC140959 mRNA Translation: AAI40960.1
CCDSiCCDS51023.1
RefSeqiNP_033944.2, NM_009814.3
UniGeneiMm.15343

Genome annotation databases

EnsembliENSMUST00000029454; ENSMUSP00000029454; ENSMUSG00000027861
GeneIDi12373
KEGGimmu:12373
UCSCiuc008qrr.3 mouse

Similar proteinsi

Entry informationi

Entry nameiCASQ2_MOUSE
AccessioniPrimary (citable) accession number: O09161
Secondary accession number(s): O88505, Q56A03
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: March 28, 2018
This is version 125 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health