CASQ2_HUMAN
ID CASQ2_HUMAN Reviewed; 399 AA.
AC O14958; B2R7M6; B4DIB0; Q5T1D2; Q8TBW8;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2002, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Calsequestrin-2;
DE AltName: Full=Calsequestrin, cardiac muscle isoform;
DE Flags: Precursor;
GN Name=CASQ2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RA Tanaka T., Inazawa J., Nakamura Y.;
RT "Molecular cloning of a human cDNA for cardiac calsequestrin and its
RT chromosomal assignment to 1p13.3 by fluorescence in situ hybridization.";
RL Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP PHOSPHORYLATION AT SER-385 AND SER-393, FUNCTION, AND SUBUNIT.
RX PubMed=21416293; DOI=10.1007/s11010-011-0787-4;
RA Sanchez E.J., Munske G.R., Criswell A., Milting H., Dunker A.K., Kang C.;
RT "Phosphorylation of human calsequestrin: implications for calcium
RT regulation.";
RL Mol. Cell. Biochem. 353:195-204(2011).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) OF 22-399, SUBUNIT, FUNCTION,
RP CHARACTERIZATION OF VARIANTS CPVT2 GLN-33; HIS-167 AND HIS-307, AND
RP CHARACTERIZATION OF VARIANTS ALA-66 AND MET-76.
RX PubMed=17881003; DOI=10.1016/j.jmb.2007.08.055;
RA Kim E., Youn B., Kemper L., Campbell C., Milting H., Varsanyi M., Kang C.;
RT "Characterization of human cardiac calsequestrin and its deleterious
RT mutants.";
RL J. Mol. Biol. 373:1047-1057(2007).
RN [9]
RP VARIANT CPVT2 HIS-307.
RX PubMed=11704930; DOI=10.1086/324565;
RA Lahat H., Pras E., Olender T., Avidan N., Ben-Asher E., Man O.,
RA Levy-Nissenbaum E., Khoury A., Lorber A., Goldman B., Lancet D., Eldar M.;
RT "A missense mutation in a highly conserved region of CASQ2 is associated
RT with autosomal recessive catecholamine-induced polymorphic ventricular
RT tachycardia in Bedouin families from Israel.";
RL Am. J. Hum. Genet. 69:1378-1384(2001).
RN [10]
RP VARIANTS ALA-66 AND MET-76.
RX PubMed=14571276; DOI=10.1038/sj.ejhg.5201061;
RA Laitinen P.J., Swan H., Kontula K.;
RT "Molecular genetics of exercise-induced polymorphic ventricular
RT tachycardia: identification of three novel cardiac ryanodine receptor
RT mutations and two common calsequestrin 2 amino-acid polymorphisms.";
RL Eur. J. Hum. Genet. 11:888-891(2003).
RN [11]
RP CHARACTERIZATION OF VARIANT CPVT2 HIS-307, INTERACTION WITH ASPH AND TRDN,
RP GLYCOSYLATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15485681; DOI=10.1016/j.cardiores.2004.09.009;
RA Houle T.D., Ram M.L., Cala S.E.;
RT "Calsequestrin mutant D307H exhibits depressed binding to its protein
RT targets and a depressed response to calcium.";
RL Cardiovasc. Res. 64:227-233(2004).
RN [12]
RP VARIANT CPVT2 HIS-167, CHARACTERIZATION OF VARIANT CPVT2 HIS-167, AND
RP FUNCTION.
RX PubMed=16908766; DOI=10.1161/circulationaha.106.623793;
RA di Barletta M.R., Viatchenko-Karpinski S., Nori A., Memmi M., Terentyev D.,
RA Turcato F., Valle G., Rizzi N., Napolitano C., Gyorke S., Volpe P.,
RA Priori S.G.;
RT "Clinical phenotype and functional characterization of CASQ2 mutations
RT associated with catecholaminergic polymorphic ventricular tachycardia.";
RL Circulation 114:1012-1019(2006).
RN [13]
RP VARIANTS CPVT2 GLN-33 AND HIS-167, CHARACTERIZATION OF VARIANTS CPVT2
RP GLN-33 AND HIS-167, AND FUNCTION.
RX PubMed=18399795; DOI=10.1042/bj20080163;
RA Valle G., Galla D., Nori A., Priori S.G., Gyorke S., de Filippis V.,
RA Volpe P.;
RT "Catecholaminergic polymorphic ventricular tachycardia-related mutations
RT R33Q and L167H alter calcium sensitivity of human cardiac calsequestrin.";
RL Biochem. J. 413:291-303(2008).
RN [14]
RP VARIANT CPVT2 ARG-180.
RX PubMed=27157848; DOI=10.1016/j.hrthm.2016.05.004;
RA Gray B., Bagnall R.D., Lam L., Ingles J., Turner C., Haan E., Davis A.,
RA Yang P.C., Clancy C.E., Sy R.W., Semsarian C.;
RT "A novel heterozygous mutation in cardiac calsequestrin causes autosomal
RT dominant catecholaminergic polymorphic ventricular tachycardia.";
RL Heart Rhythm 13:1652-1660(2016).
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:16908766, ECO:0000269|PubMed:17881003,
CC ECO:0000269|PubMed:18399795, ECO:0000269|PubMed:21416293}.
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.
CC {ECO:0000269|PubMed:15485681, ECO:0000269|PubMed:17881003,
CC ECO:0000269|PubMed:21416293}.
CC -!- INTERACTION:
CC O14958; Q13895: BYSL; NbExp=3; IntAct=EBI-6859557, EBI-358049;
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:O09161}. Note=This isoform of calsequestrin
CC occurs in the sarcoplasmic reticulum's terminal cisternae luminal
CC spaces of cardiac and slow skeletal muscle cells.
CC {ECO:0000250|UniProtKB:O09161}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O14958-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14958-2; Sequence=VSP_056477;
CC -!- PTM: Phosphorylation in the C-terminus, probably by CK2, moderately
CC increases calcium buffering capacity. {ECO:0000269|PubMed:21416293}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15485681}.
CC -!- DISEASE: Ventricular tachycardia, catecholaminergic polymorphic, 2
CC (CPVT2) [MIM:611938]: An arrhythmogenic disorder characterized by
CC stress-induced, bidirectional ventricular tachycardia that may
CC degenerate into cardiac arrest and cause sudden death. Patients present
CC with recurrent syncope, seizures, or sudden death after physical
CC activity or emotional stress. CPVT2 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:11704930, ECO:0000269|PubMed:15485681,
CC ECO:0000269|PubMed:16908766, ECO:0000269|PubMed:17881003,
CC ECO:0000269|PubMed:18399795, ECO:0000269|PubMed:27157848}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the calsequestrin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Calsequestrin entry;
CC URL="https://en.wikipedia.org/wiki/Calsequestrin";
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DR EMBL; D55655; BAA23494.1; -; mRNA.
DR EMBL; AK295502; BAG58422.1; -; mRNA.
DR EMBL; AK313041; BAG35873.1; -; mRNA.
DR EMBL; AL449264; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL450389; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56635.1; -; Genomic_DNA.
DR EMBL; BC022288; AAH22288.1; -; mRNA.
DR CCDS; CCDS884.1; -. [O14958-1]
DR RefSeq; NP_001223.2; NM_001232.3. [O14958-1]
DR PDB; 2VAF; X-ray; 3.80 A; A=22-399.
DR PDB; 6OWV; X-ray; 1.88 A; A=18-399.
DR PDB; 6OWW; X-ray; 3.84 A; A/B/C/D/E/F/G/H=18-399.
DR PDBsum; 2VAF; -.
DR PDBsum; 6OWV; -.
DR PDBsum; 6OWW; -.
DR AlphaFoldDB; O14958; -.
DR SMR; O14958; -.
DR BioGRID; 107295; 63.
DR IntAct; O14958; 44.
DR STRING; 9606.ENSP00000261448; -.
DR DrugBank; DB11093; Calcium citrate.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR TCDB; 8.A.88.1.5; the calciquestrin (casq) family.
DR GlyGen; O14958; 1 site.
DR iPTMnet; O14958; -.
DR PhosphoSitePlus; O14958; -.
DR BioMuta; CASQ2; -.
DR jPOST; O14958; -.
DR MassIVE; O14958; -.
DR PaxDb; O14958; -.
DR PeptideAtlas; O14958; -.
DR PRIDE; O14958; -.
DR ProteomicsDB; 4290; -.
DR ProteomicsDB; 48335; -. [O14958-1]
DR Antibodypedia; 20176; 310 antibodies from 30 providers.
DR DNASU; 845; -.
DR Ensembl; ENST00000261448.6; ENSP00000261448.5; ENSG00000118729.12. [O14958-1]
DR GeneID; 845; -.
DR KEGG; hsa:845; -.
DR MANE-Select; ENST00000261448.6; ENSP00000261448.5; NM_001232.4; NP_001223.2.
DR UCSC; uc001efx.5; human. [O14958-1]
DR CTD; 845; -.
DR DisGeNET; 845; -.
DR GeneCards; CASQ2; -.
DR GeneReviews; CASQ2; -.
DR HGNC; HGNC:1513; CASQ2.
DR HPA; ENSG00000118729; Tissue enriched (heart).
DR MalaCards; CASQ2; -.
DR MIM; 114251; gene.
DR MIM; 611938; phenotype.
DR neXtProt; NX_O14958; -.
DR OpenTargets; ENSG00000118729; -.
DR Orphanet; 3286; Catecholaminergic polymorphic ventricular tachycardia.
DR PharmGKB; PA26096; -.
DR VEuPathDB; HostDB:ENSG00000118729; -.
DR eggNOG; ENOG502QU4Q; Eukaryota.
DR GeneTree; ENSGT00390000019377; -.
DR HOGENOM; CLU_036303_1_0_1; -.
DR InParanoid; O14958; -.
DR OMA; FEIWEDD; -.
DR OrthoDB; 1091027at2759; -.
DR PhylomeDB; O14958; -.
DR TreeFam; TF313796; -.
DR PathwayCommons; O14958; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR SignaLink; O14958; -.
DR SIGNOR; O14958; -.
DR BioGRID-ORCS; 845; 17 hits in 1076 CRISPR screens.
DR ChiTaRS; CASQ2; human.
DR EvolutionaryTrace; O14958; -.
DR GenomeRNAi; 845; -.
DR Pharos; O14958; Tbio.
DR PRO; PR:O14958; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O14958; protein.
DR Bgee; ENSG00000118729; Expressed in heart right ventricle and 143 other tissues.
DR Genevisible; O14958; HS.
DR GO; GO:0034704; C:calcium channel complex; TAS:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0014701; C:junctional sarcoplasmic reticulum membrane; TAS:BHF-UCL.
DR GO; GO:0016529; C:sarcoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0033018; C:sarcoplasmic reticulum lumen; IBA:GO_Central.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0030018; C:Z disc; ISS:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0140314; F:calcium ion sequestering activity; IMP:BHF-UCL.
DR GO; GO:0048306; F:calcium-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:BHF-UCL.
DR GO; GO:0060048; P:cardiac muscle contraction; IMP:BHF-UCL.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:BHF-UCL.
DR GO; GO:0071313; P:cellular response to caffeine; IMP:BHF-UCL.
DR GO; GO:0005513; P:detection of calcium ion; TAS:BHF-UCL.
DR GO; GO:1901017; P:negative regulation of potassium ion transmembrane transporter activity; ISS:BHF-UCL.
DR GO; GO:0043267; P:negative regulation of potassium ion transport; ISS:BHF-UCL.
DR GO; GO:0060315; P:negative regulation of ryanodine-sensitive calcium-release channel activity; IDA:BHF-UCL.
DR GO; GO:0051258; P:protein polymerization; IDA:UniProtKB.
DR GO; GO:0086029; P:Purkinje myocyte to ventricular cardiac muscle cell signaling; NAS:BHF-UCL.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; IMP:BHF-UCL.
DR GO; GO:0010649; P:regulation of cell communication by electrical coupling; IMP:BHF-UCL.
DR GO; GO:0002027; P:regulation of heart rate; IMP:UniProtKB.
DR GO; GO:0060306; P:regulation of membrane repolarization; ISS:BHF-UCL.
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; ISS:BHF-UCL.
DR GO; GO:0051208; P:sequestering of calcium ion; IDA:BHF-UCL.
DR GO; GO:0006941; P:striated muscle contraction; TAS:ProtInc.
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 DisProt; DP02630; -.
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 3D-structure; Alternative splicing; Calcium; Disease variant; Glycoprotein;
KW Metal-binding; Muscle protein; Phosphoprotein; Reference proteome;
KW Sarcoplasmic reticulum; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000250"
FT CHAIN 20..399
FT /note="Calsequestrin-2"
FT /id="PRO_0000004218"
FT REGION 365..399
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 370..399
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 282
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O09161"
FT MOD_RES 385
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21416293"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21416293"
FT CARBOHYD 335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 107..178
FT /note="GFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVEIISSKLEVQAF
FT ERIEDYIKLIGFFKSEDSEY -> D (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056477"
FT VARIANT 33
FT /note="R -> Q (in CPVT2; reduces calcium-dependent
FT dimerization; dbSNP:rs749547712)"
FT /evidence="ECO:0000269|PubMed:17881003,
FT ECO:0000269|PubMed:18399795"
FT /id="VAR_055234"
FT VARIANT 66
FT /note="T -> A (no effect on calcium-binding and calcium-
FT dependent dimerization; dbSNP:rs4074536)"
FT /evidence="ECO:0000269|PubMed:14571276,
FT ECO:0000269|PubMed:17881003"
FT /id="VAR_023692"
FT VARIANT 76
FT /note="V -> M (increases dimerization in the absence of
FT calcium; dbSNP:rs10801999)"
FT /evidence="ECO:0000269|PubMed:14571276,
FT ECO:0000269|PubMed:17881003"
FT /id="VAR_023693"
FT VARIANT 167
FT /note="L -> H (in CPVT2; alters protein folding; reduces
FT calcium-binding; reduces calcium-dependent oligomerization;
FT decreases sarcoplasmic reticulum Ca(2+) storing capacity;
FT reduces the amplitude of I(Ca)-induced Ca(2+) transients;
FT reduces spontaneous Ca(2+) sparks in permeabilized
FT myocytes; dbSNP:rs121434550)"
FT /evidence="ECO:0000269|PubMed:16908766,
FT ECO:0000269|PubMed:17881003, ECO:0000269|PubMed:18399795"
FT /id="VAR_044118"
FT VARIANT 180
FT /note="K -> R (in CPVT2; dbSNP:rs886039816)"
FT /evidence="ECO:0000269|PubMed:27157848"
FT /id="VAR_076546"
FT VARIANT 244
FT /note="H -> R (in dbSNP:rs28730716)"
FT /id="VAR_067036"
FT VARIANT 307
FT /note="D -> H (in CPVT2; reduces calcium-binding; impairs
FT calcium-dependent oligomerization; causes 50% decrease in
FT calcium-dependent binding to TRDN; causes 50% decrease in
FT calcium-dependent binding to ASPH; dbSNP:rs121434549)"
FT /evidence="ECO:0000269|PubMed:11704930,
FT ECO:0000269|PubMed:15485681, ECO:0000269|PubMed:17881003"
FT /id="VAR_016075"
FT VARIANT 335
FT /note="N -> K (in dbSNP:rs28730712)"
FT /id="VAR_067037"
FT CONFLICT 67
FT /note="Q -> P (in Ref. 1; BAA23494)"
FT /evidence="ECO:0000305"
FT CONFLICT 175
FT /note="D -> G (in Ref. 2; BAG35873)"
FT /evidence="ECO:0000305"
FT HELIX 41..48
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 50..56
FT /evidence="ECO:0007829|PDB:6OWV"
FT HELIX 71..83
FT /evidence="ECO:0007829|PDB:6OWV"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 87..94
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:6OWV"
FT HELIX 100..106
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 114..118
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:6OWV"
FT HELIX 131..142
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:6OWV"
FT HELIX 152..160
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:6OWV"
FT HELIX 177..188
FT /evidence="ECO:0007829|PDB:6OWV"
FT TURN 189..192
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 193..198
FT /evidence="ECO:0007829|PDB:6OWV"
FT HELIX 201..206
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 214..217
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:6OWV"
FT HELIX 234..243
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 248..251
FT /evidence="ECO:0007829|PDB:6OWV"
FT TURN 254..256
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:6OWV"
FT HELIX 279..294
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 303..306
FT /evidence="ECO:0007829|PDB:6OWV"
FT TURN 308..310
FT /evidence="ECO:0007829|PDB:6OWV"
FT HELIX 312..322
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 330..334
FT /evidence="ECO:0007829|PDB:6OWV"
FT TURN 336..338
FT /evidence="ECO:0007829|PDB:6OWV"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:6OWV"
FT HELIX 355..367
FT /evidence="ECO:0007829|PDB:6OWV"
SQ SEQUENCE 399 AA; 46436 MW; 7794DC2FF7E4B064 CRC64;
MKRTHLFIVG IYFLSSCRAE EGLNFPTYDG KDRVVSLSEK NFKQVLKKYD LLCLYYHEPV
SSDKVTQKQF QLKEIVLELV AQVLEHKAIG FVMVDAKKEA KLAKKLGFDE EGSLYILKGD
RTIEFDGEFA ADVLVEFLLD LIEDPVEIIS SKLEVQAFER IEDYIKLIGF FKSEDSEYYK
AFEEAAEHFQ PYIKFFATFD KGVAKKLSLK MNEVDFYEPF MDEPIAIPNK PYTEEELVEF
VKEHQRPTLR RLRPEEMFET WEDDLNGIHI VAFAEKSDPD GYEFLEILKQ VARDNTDNPD
LSILWIDPDD FPLLVAYWEK TFKIDLFRPQ IGVVNVTDAD SVWMEIPDDD DLPTAEELED
WIEDVLSGKI NTEDDDEDDD DDDNSDEEDN DDSDDDDDE
