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 27-MAR-2024, entry version 198. 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7F05; X-ray; 2.30 A; A/B/C/D=20-399. DR PDBsum; 2VAF; -. DR PDBsum; 6OWV; -. DR PDBsum; 6OWW; -. DR PDBsum; 7F05; -. DR AlphaFoldDB; O14958; -. DR SMR; O14958; -. DR BioGRID; 107295; 65. DR IntAct; O14958; 45. DR MINT; O14958; -. 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 GlyCosmos; O14958; 1 site, No reported glycans. DR GlyGen; O14958; 1 site. DR iPTMnet; O14958; -. DR PhosphoSitePlus; O14958; -. DR BioMuta; CASQ2; -. DR jPOST; O14958; -. DR MassIVE; O14958; -. DR PaxDb; 9606-ENSP00000261448; -. DR PeptideAtlas; O14958; -. DR ProteomicsDB; 4290; -. DR ProteomicsDB; 48335; -. [O14958-1] DR Antibodypedia; 20176; 327 antibodies from 30 providers. DR DNASU; 845; -. DR Ensembl; ENST00000261448.6; ENSP00000261448.5; ENSG00000118729.13. [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 AGR; HGNC:1513; -. 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; 2873811at2759; -. 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; 18 hits in 1154 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 145 other cell types or tissues. 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; IDA:DisProt. DR GO; GO:0048306; F:calcium-dependent protein binding; IDA:UniProtKB. DR GO; GO:0043167; F:ion binding; IDA:DisProt. 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:0071313; P:cellular response to caffeine; IMP:BHF-UCL. DR GO; GO:0005513; P:detection of calcium ion; TAS:BHF-UCL. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IMP: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: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 Gene3D; 3.40.30.10; Glutaredoxin; 3. 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 PANTHER; PTHR10033; CALSEQUESTRIN; 1. DR PANTHER; PTHR10033:SF15; CALSEQUESTRIN-2; 1. DR Pfam; PF01216; Calsequestrin; 1. DR PRINTS; PR00312; CALSEQUESTRN. DR SUPFAM; SSF52833; Thioredoxin-like; 3. DR PROSITE; PS00863; CALSEQUESTRIN_1; 1. DR PROSITE; PS00864; CALSEQUESTRIN_2; 1. DR Genevisible; O14958; HS. 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 FT calcium-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 HELIX 257..261 FT /evidence="ECO:0007829|PDB:7F05" FT STRAND 269..273 FT /evidence="ECO:0007829|PDB:6OWV" FT HELIX 279..294 FT /evidence="ECO:0007829|PDB:6OWV" FT TURN 295..297 FT /evidence="ECO:0007829|PDB:7F05" 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 //