CASQ2_MOUSE
ID CASQ2_MOUSE Reviewed; 415 AA.
AC O09161; O88505; Q56A03;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Calsequestrin-2;
DE AltName: Full=Calsequestrin, cardiac muscle isoform;
DE Flags: Precursor;
GN Name=Casq2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=9795116; DOI=10.1016/s0378-1119(98)00372-2;
RA Park K.-W., Goo J.H., Chung H.-S., Kim H., Kim D.-H., Park W.-J.;
RT "Cloning of the genes encoding mouse cardiac and skeletal calsequestrins:
RT expression pattern during embryogenesis.";
RL Gene 217:25-30(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RA Sato Y., Ferguson D.G., Sako H., Dorn G.W. II, Kadambi V.J., Yatani A.,
RA Hoit B.D., Walsh R.A., Kranias E.G.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=16932808; DOI=10.1172/jci29128;
RA Knollmann B.C., Chopra N., Hlaing T., Akin B., Yang T., Ettensohn K.,
RA Knollmann B.E., Horton K.D., Weissman N.J., Holinstat I., Zhang W.,
RA Roden D.M., Jones L.R., Franzini-Armstrong C., Pfeifer K.;
RT "Casq2 deletion causes sarcoplasmic reticulum volume increase, premature
RT Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia.";
RL J. Clin. Invest. 116:2510-2520(2006).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, AND MUTAGENESIS OF ASP-307.
RX PubMed=17607358; DOI=10.1172/jci31080;
RA Song L., Alcalai R., Arad M., Wolf C.M., Toka O., Conner D.A., Berul C.I.,
RA Eldar M., Seidman C.E., Seidman J.G.;
RT "Calsequestrin 2 (CASQ2) mutations increase expression of calreticulin and
RT ryanodine receptors, causing catecholaminergic polymorphic ventricular
RT tachycardia.";
RL J. Clin. Invest. 117:1814-1823(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-282, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-307, AND TISSUE
RP SPECIFICITY.
RX PubMed=19920148; DOI=10.1074/jbc.m109.053892;
RA Kalyanasundaram A., Bal N.C., Franzini-Armstrong C., Knollmann B.C.,
RA Periasamy M.;
RT "The calsequestrin mutation CASQ2D307H does not affect protein stability
RT and targeting to the junctional sarcoplasmic reticulum but compromises its
RT dynamic regulation of calcium buffering.";
RL J. Biol. Chem. 285:3076-3083(2010).
CC -!- FUNCTION: Calsequestrin is a high-capacity, moderate affinity, calcium-
CC binding protein and thus acts as an internal calcium store in muscle.
CC Calcium ions are bound by clusters of acidic residues at the protein
CC surface, especially at the interface between subunits. Can bind around
CC 60 Ca(2+) ions. Regulates the release of lumenal Ca(2+) via the calcium
CC release channel RYR2; this plays an important role in triggering muscle
CC contraction. Plays a role in excitation-contraction coupling in the
CC heart and in regulating the rate of heart beats.
CC {ECO:0000269|PubMed:16932808, ECO:0000269|PubMed:17607358,
CC ECO:0000269|PubMed:19920148}.
CC -!- SUBUNIT: Monomer, homodimer and homooligomer. Mostly monomeric in the
CC absence of calcium. Forms higher oligomers in a calcium-dependent
CC manner. Dimers associate to form tetramers, that then form linear
CC homomer chains. Interacts with ASPH and TRDN (By similarity).
CC {ECO:0000250|UniProtKB:O14958}.
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum lumen
CC {ECO:0000269|PubMed:16932808, ECO:0000269|PubMed:19920148}. Note=This
CC isoform of calsequestrin occurs in the sarcoplasmic reticulum's
CC terminal cisternae luminal spaces of cardiac and slow skeletal muscle
CC cells. {ECO:0000269|PubMed:16932808, ECO:0000269|PubMed:19920148}.
CC -!- TISSUE SPECIFICITY: Detected in heart (at protein level). Detected in
CC heart. {ECO:0000269|PubMed:16932808, ECO:0000269|PubMed:19920148,
CC ECO:0000269|PubMed:9795116}.
CC -!- PTM: Phosphorylation in the C-terminus moderately increases calcium
CC buffering capacity. {ECO:0000250|UniProtKB:O14958}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:O14958}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
CC rate, are viable and display normal sarcoplasmic calcium release and
CC normal heart function under basal conditions, but have a slower heart
CC rate. Mutant mice are subject to polymorphic arrhythmia after exercise
CC and to catecholaminergic ventricular arrhythmia, and their myocytes
CC show increased Ca(2+) release in response to isoproterenol. Besides,
CC the volume of the junctional sarcoplasmic reticulum is increased, and
CC it seems to lack visible content. {ECO:0000269|PubMed:16932808,
CC ECO:0000269|PubMed:17607358}.
CC -!- SIMILARITY: Belongs to the calsequestrin family. {ECO:0000305}.
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DR EMBL; U91483; AAC82512.1; -; mRNA.
DR EMBL; AF068244; AAC69472.1; -; mRNA.
DR EMBL; CH466608; EDL07619.1; -; Genomic_DNA.
DR EMBL; BC092229; AAH92229.1; -; mRNA.
DR EMBL; BC140959; AAI40960.1; -; mRNA.
DR CCDS; CCDS51023.1; -.
DR RefSeq; NP_033944.2; NM_009814.3.
DR AlphaFoldDB; O09161; -.
DR SMR; O09161; -.
DR STRING; 10090.ENSMUSP00000029454; -.
DR GlyGen; O09161; 1 site.
DR iPTMnet; O09161; -.
DR PhosphoSitePlus; O09161; -.
DR MaxQB; O09161; -.
DR PaxDb; O09161; -.
DR PRIDE; O09161; -.
DR ProteomicsDB; 265441; -.
DR Antibodypedia; 20176; 310 antibodies from 30 providers.
DR DNASU; 12373; -.
DR Ensembl; ENSMUST00000029454; ENSMUSP00000029454; ENSMUSG00000027861.
DR GeneID; 12373; -.
DR KEGG; mmu:12373; -.
DR UCSC; uc008qrr.3; mouse.
DR CTD; 845; -.
DR MGI; MGI:1309469; Casq2.
DR VEuPathDB; HostDB:ENSMUSG00000027861; -.
DR eggNOG; ENOG502QU4Q; Eukaryota.
DR GeneTree; ENSGT00390000019377; -.
DR HOGENOM; CLU_036303_1_0_1; -.
DR InParanoid; O09161; -.
DR OMA; FEIWEDD; -.
DR TreeFam; TF313796; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR Reactome; R-MMU-5578775; Ion homeostasis.
DR BioGRID-ORCS; 12373; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Casq2; mouse.
DR PRO; PR:O09161; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; O09161; protein.
DR Bgee; ENSMUSG00000027861; Expressed in myocardium of ventricle and 184 other tissues.
DR ExpressionAtlas; O09161; baseline and differential.
DR Genevisible; O09161; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030314; C:junctional membrane complex; IDA:UniProtKB.
DR GO; GO:0016529; C:sarcoplasmic reticulum; ISO:MGI.
DR GO; GO:0033018; C:sarcoplasmic reticulum lumen; IDA:UniProtKB.
DR GO; GO:0030018; C:Z disc; IDA:MGI.
DR GO; GO:0005509; F:calcium ion binding; IMP:UniProtKB.
DR GO; GO:0140314; F:calcium ion sequestering activity; ISO:MGI.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0005080; F:protein kinase C binding; ISO:MGI.
DR GO; GO:0060048; P:cardiac muscle contraction; ISO:MGI.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:MGI.
DR GO; GO:0071313; P:cellular response to caffeine; ISO:MGI.
DR GO; GO:1901017; P:negative regulation of potassium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0043267; P:negative regulation of potassium ion transport; IDA:BHF-UCL.
DR GO; GO:0060315; P:negative regulation of ryanodine-sensitive calcium-release channel activity; ISO:MGI.
DR GO; GO:0051258; P:protein polymerization; ISO:MGI.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; ISO:MGI.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; IDA:MGI.
DR GO; GO:0010649; P:regulation of cell communication by electrical coupling; ISO:MGI.
DR GO; GO:0002027; P:regulation of heart rate; IMP:UniProtKB.
DR GO; GO:0060306; P:regulation of membrane repolarization; IDA:BHF-UCL.
DR GO; GO:0006937; P:regulation of muscle contraction; TAS:MGI.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IBA:GO_Central.
DR GO; GO:0010880; P:regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IMP:UniProtKB.
DR GO; GO:0045214; P:sarcomere organization; IMP:UniProtKB.
DR GO; GO:0051208; P:sequestering of calcium ion; ISO:MGI.
DR CDD; cd03074; PDI_b'_Calsequestrin_C; 1.
DR CDD; cd03066; PDI_b_Calsequestrin_middle; 1.
DR CDD; cd03065; PDI_b_Calsequestrin_N; 1.
DR InterPro; IPR001393; Calsequestrin.
DR InterPro; IPR041860; Calsequestrin_C.
DR InterPro; IPR018233; Calsequestrin_CS.
DR InterPro; IPR041858; Calsequestrin_middle_dom.
DR InterPro; IPR041859; Calsequestrin_N.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR Pfam; PF01216; Calsequestrin; 1.
DR SUPFAM; SSF52833; SSF52833; 3.
DR PROSITE; PS00863; CALSEQUESTRIN_1; 1.
DR PROSITE; PS00864; CALSEQUESTRIN_2; 1.
PE 1: Evidence at protein level;
KW Calcium; Glycoprotein; Metal-binding; Muscle protein; Phosphoprotein;
KW Reference proteome; Sarcoplasmic reticulum; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..415
FT /note="Calsequestrin-2"
FT /id="PRO_0000004219"
FT REGION 366..415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 373..415
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 282
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 307
FT /note="D->H: Impairs calcium-dependent oligomerization and
FT promotes ventricular tachycardia."
FT /evidence="ECO:0000269|PubMed:17607358,
FT ECO:0000269|PubMed:19920148"
FT CONFLICT 1..2
FT /note="MK -> MER (in Ref. 1; AAC82512)"
FT /evidence="ECO:0000305"
FT CONFLICT 20
FT /note="E -> Q (in Ref. 1; AAC82512)"
FT /evidence="ECO:0000305"
FT CONFLICT 278
FT /note="D -> H (in Ref. 1; AAC82512)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 415 AA; 48176 MW; 82D7680878A6E3B5 CRC64;
MKRIYLLMVG VYLLSLSGAE EGLNFPTYDG KDRVVSLSEK NLKQMLKRYD LLCLYYHEPV
SSDKVSQKQF QLKEIVLELV AQVLEHKNIG FVMVDSRKEA KLAKRLGFSE EGSLYVLKGD
RTIEFDGEFA ADVLVEFLLD LIEDPVEIVN NKLEVQAFER IEDQTKLLGF FKNEDSEYYK
AFQEAAEHFQ PYIKFFATFD KAVAKKLSLK MNEVGFYEPF MDEPNVIPNK PYTEEELVEF
VKEHQRPTLR RLRPEDMFET WEDDLNGIHI VAFAEKSDPD GYEFLEILKQ VARDNTDNPD
LSILWIDPDD FPLLVAYWEK TFKIDLFKPQ IGVVNVTDAD SIWMEIPDDD DLPTAEELED
WIEDVLSGKI NTEDDDNEDE DDDGDDNDDD DDDDDDNDNS DEDNEDSDDD DDDDE
