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Protein

Calsequestrin-2

Gene

Casq2

Organism
Mus musculus (Mouse)
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.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: UniProtKB
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Muscle protein

Keywords - Ligandi

Calcium, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1309469. Casq2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • intracellular Source: MGI
  • junctional membrane complex Source: UniProtKB
  • sarcoplasmic reticulum Source: MGI
  • sarcoplasmic reticulum lumen Source: UniProtKB
  • Z disc Source: MGI
Complete GO annotation...

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 arrhytmia after exercise and to catecholaminergic ventricular arrhytmia, 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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi307 – 3071D → H: Impairs calcium-dependent oligomerization and promotes ventricular tachycardia. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence analysisAdd
BLAST
Chaini20 – 415396Calsequestrin-2PRO_0000004219Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei282 – 2821PhosphotyrosineCombined sources
Glycosylationi335 – 3351N-linked (GlcNAc...)Sequence analysis

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.
PhosphoSiteiO09161.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiO09161.
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 interaction.
MINTiMINT-4089876.
STRINGi10090.ENSMUSP00000029454.

Structurei

3D structure databases

ProteinModelPortaliO09161.
SMRiO09161. Positions 22-370.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi373 – 41543Asp/Glu-rich (acidic)Add
BLAST

Sequence similaritiesi

Belongs to the calsequestrin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IGY5. Eukaryota.
ENOG4111R2M. LUCA.
GeneTreeiENSGT00390000019377.
HOVERGENiHBG050805.
InParanoidiO09161.
OrthoDBiEOG725DHM.
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]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1 – 22MK → MER in AAC82512 (PubMed:9795116).Curated
Sequence conflicti20 – 201E → Q in AAC82512 (PubMed:9795116).Curated
Sequence conflicti278 – 2781D → H in AAC82512 (PubMed:9795116).Curated

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliO09161.
SMRiO09161. Positions 22-370.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO09161. 1 interaction.
MINTiMINT-4089876.
STRINGi10090.ENSMUSP00000029454.

PTM databases

iPTMnetiO09161.
PhosphoSiteiO09161.

Proteomic databases

MaxQBiO09161.
PaxDbiO09161.
PRIDEiO09161.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi845.
MGIiMGI:1309469. Casq2.

Phylogenomic databases

eggNOGiENOG410IGY5. Eukaryota.
ENOG4111R2M. LUCA.
GeneTreeiENSGT00390000019377.
HOVERGENiHBG050805.
InParanoidiO09161.
OrthoDBiEOG725DHM.
TreeFamiTF313796.

Enzyme and pathway databases

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

Miscellaneous databases

PROiO09161.
SOURCEiSearch...

Gene expression databases

BgeeiO09161.
CleanExiMM_CASQ2.
ExpressionAtlasiO09161. baseline and differential.
GenevisibleiO09161. MM.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of the genes encoding mouse cardiac and skeletal calsequestrins: expression pattern during embryogenesis."
    Park K.-W., Goo J.H., Chung H.-S., Kim H., Kim D.-H., Park W.-J.
    Gene 217:25-30(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
  2. Sato Y., Ferguson D.G., Sako H., Dorn G.W. II, Kadambi V.J., Yatani A., Hoit B.D., Walsh R.A., Kranias E.G.
    Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/cJ.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Brain and Eye.
  5. "Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia."
    Knollmann B.C., Chopra N., Hlaing T., Akin B., Yang T., Ettensohn K., Knollmann B.E., Horton K.D., Weissman N.J., Holinstat I., Zhang W., Roden D.M., Jones L.R., Franzini-Armstrong C., Pfeifer K.
    J. Clin. Invest. 116:2510-2520(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  6. "Calsequestrin 2 (CASQ2) mutations increase expression of calreticulin and ryanodine receptors, causing catecholaminergic polymorphic ventricular tachycardia."
    Song L., Alcalai R., Arad M., Wolf C.M., Toka O., Conner D.A., Berul C.I., Eldar M., Seidman C.E., Seidman J.G.
    J. Clin. Invest. 117:1814-1823(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION, MUTAGENESIS OF ASP-307.
  7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-282, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brown adipose tissue, Heart, Lung and Testis.
  8. "The calsequestrin mutation CASQ2D307H does not affect protein stability and targeting to the junctional sarcoplasmic reticulum but compromises its dynamic regulation of calcium buffering."
    Kalyanasundaram A., Bal N.C., Franzini-Armstrong C., Knollmann B.C., Periasamy M.
    J. Biol. Chem. 285:3076-3083(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-307, TISSUE SPECIFICITY.

Entry informationi

Entry nameiCASQ2_MOUSE
AccessioniPrimary (citable) accession number: O09161
Secondary accession number(s): O88505, Q56A03
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: June 8, 2016
This is version 118 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.