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 13-FEB-2019, entry version 170. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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., RA 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., RA 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., RA Eldar M.; RT "A missense mutation in a highly conserved region of CASQ2 is RT associated with autosomal recessive catecholamine-induced polymorphic RT ventricular 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 RP TRDN, 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., RA Terentyev D., Turcato F., Valle G., Rizzi N., Napolitano C., RA Gyorke S., Volpe P., Priori S.G.; RT "Clinical phenotype and functional characterization of CASQ2 mutations RT associated with catecholaminergic polymorphic ventricular RT 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 RT mutations R33Q and L167H alter calcium sensitivity of human cardiac RT 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., RA Davis A., Yang P.C., Clancy C.E., Sy R.W., Semsarian C.; RT "A novel heterozygous mutation in cardiac calsequestrin causes RT autosomal dominant catecholaminergic polymorphic ventricular RT tachycardia."; RL Heart Rhythm 13:1652-1660(2016). CC -!- FUNCTION: Calsequestrin is a high-capacity, moderate affinity, CC calcium-binding protein and thus acts as an internal calcium store CC in muscle. Calcium ions are bound by clusters of acidic residues CC at the protein surface, especially at the interface between CC subunits. Can bind around 60 Ca(2+) ions. Regulates the release of CC lumenal Ca(2+) via the calcium release channel RYR2; this plays an CC important role in triggering muscle contraction. Plays a role in CC excitation-contraction coupling in the heart and in regulating the CC rate of heart beats. {ECO:0000269|PubMed:16908766, CC ECO:0000269|PubMed:17881003, ECO:0000269|PubMed:18399795, CC ECO:0000269|PubMed:21416293}. CC -!- SUBUNIT: Monomer, homodimer and homooligomer. Mostly monomeric in CC the absence of calcium. Forms higher oligomers in a calcium- CC dependent manner. Dimers associate to form tetramers, that then CC form linear homopolymer chains. Interacts with ASPH and TRDN. CC {ECO:0000269|PubMed:15485681, ECO:0000269|PubMed:17881003, CC ECO:0000269|PubMed:21416293}. 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 Note=No experimental confirmation available.; CC -!- PTM: Phosphorylation in the C-terminus, probably by CK2, CC moderately increases calcium buffering capacity. CC {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 CC present with recurrent syncope, seizures, or sudden death after CC physical activity or emotional stress. CPVT2 inheritance is CC autosomal recessive. {ECO:0000269|PubMed:11704930, CC ECO:0000269|PubMed:15485681, ECO:0000269|PubMed:16908766, CC ECO:0000269|PubMed:17881003, ECO:0000269|PubMed:18399795, CC ECO:0000269|PubMed:27157848}. Note=The disease is caused by CC mutations affecting the gene represented in this 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 UniGene; Hs.57975; -. DR PDB; 2VAF; X-ray; 3.80 A; A=22-399. DR PDBsum; 2VAF; -. DR ProteinModelPortal; O14958; -. DR SMR; O14958; -. DR BioGrid; 107295; 47. DR IntAct; O14958; 11. DR STRING; 9606.ENSP00000261448; -. DR iPTMnet; O14958; -. DR PhosphoSitePlus; O14958; -. DR BioMuta; CASQ2; -. DR jPOST; O14958; -. DR PaxDb; O14958; -. DR PeptideAtlas; O14958; -. DR PRIDE; O14958; -. DR ProteomicsDB; 48335; -. DR DNASU; 845; -. DR Ensembl; ENST00000261448; ENSP00000261448; ENSG00000118729. [O14958-1] DR GeneID; 845; -. DR KEGG; hsa:845; -. DR UCSC; uc001efx.5; human. [O14958-1] DR CTD; 845; -. DR DisGeNET; 845; -. DR EuPathDB; HostDB:ENSG00000118729.11; -. DR GeneCards; CASQ2; -. DR GeneReviews; CASQ2; -. DR HGNC; HGNC:1513; CASQ2. DR HPA; HPA027285; -. DR HPA; HPA055298; -. 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 eggNOG; ENOG410IGY5; Eukaryota. DR eggNOG; ENOG4111R2M; LUCA. DR GeneTree; ENSGT00390000019377; -. DR HOGENOM; HOG000049047; -. DR HOVERGEN; HBG050805; -. DR InParanoid; O14958; -. DR OMA; TEKNFKQ; -. DR OrthoDB; 1091027at2759; -. DR PhylomeDB; O14958; -. DR TreeFam; TF313796; -. DR Reactome; R-HSA-2672351; Stimuli-sensing channels. DR Reactome; R-HSA-5578775; Ion homeostasis. DR SIGNOR; O14958; -. DR ChiTaRS; CASQ2; human. DR EvolutionaryTrace; O14958; -. DR GenomeRNAi; 845; -. DR PRO; PR:O14958; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000118729; Expressed in 164 organ(s), highest expression level in myocardium. 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:0030314; C:junctional membrane complex; IEA:Ensembl. 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: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:0071313; P:cellular response to caffeine; IMP:BHF-UCL. DR GO; GO:0005513; P:detection of calcium ion; TAS:BHF-UCL. DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome. 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:1903779; P:regulation of cardiac conduction; TAS:Reactome. 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:0014809; P:regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion; IBA:GO_Central. DR GO; GO:0045214; P:sarcomere organization; IEA:Ensembl. DR GO; GO:0051208; P:sequestering of calcium ion; IDA:BHF-UCL. DR GO; GO:0006941; P:striated muscle contraction; TAS:ProtInc. DR InterPro; IPR001393; Calsequestrin. DR InterPro; IPR018233; Calsequestrin_CS. DR InterPro; IPR036249; Thioredoxin-like_sf. DR PANTHER; PTHR10033; PTHR10033; 1. 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; Complete proteome; KW Disease mutation; Glycoprotein; Metal-binding; Muscle protein; KW Phosphoprotein; Polymorphism; Reference proteome; KW Sarcoplasmic reticulum; Signal. FT SIGNAL 1 19 {ECO:0000250}. FT CHAIN 20 399 Calsequestrin-2. FT /FTId=PRO_0000004218. FT COMPBIAS 356 399 Asp/Glu-rich (acidic). FT MOD_RES 282 282 Phosphotyrosine. FT {ECO:0000250|UniProtKB:O09161}. FT MOD_RES 385 385 Phosphoserine. FT {ECO:0000269|PubMed:21416293}. FT MOD_RES 393 393 Phosphoserine. FT {ECO:0000269|PubMed:21416293}. FT CARBOHYD 335 335 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT VAR_SEQ 107 178 GFDEEGSLYILKGDRTIEFDGEFAADVLVEFLLDLIEDPVE FT IISSKLEVQAFERIEDYIKLIGFFKSEDSEY -> D (in FT isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_056477. FT VARIANT 33 33 R -> Q (in CPVT2; reduces calcium- FT dependent dimerization; FT dbSNP:rs749547712). FT {ECO:0000269|PubMed:17881003, FT ECO:0000269|PubMed:18399795}. FT /FTId=VAR_055234. FT VARIANT 66 66 T -> A (no effect on calcium-binding and FT calcium-dependent dimerization; FT dbSNP:rs4074536). FT {ECO:0000269|PubMed:14571276, FT ECO:0000269|PubMed:17881003}. FT /FTId=VAR_023692. FT VARIANT 76 76 V -> M (increases dimerization in the FT absence of calcium; dbSNP:rs10801999). FT {ECO:0000269|PubMed:14571276, FT ECO:0000269|PubMed:17881003}. FT /FTId=VAR_023693. FT VARIANT 167 167 L -> H (in CPVT2; alters protein folding; FT reduces calcium-binding; reduces calcium- FT dependent oligomerization; decreases FT sarcoplasmic reticulum Ca(2+) storing FT capacity; reduces the amplitude of I(Ca)- FT induced Ca(2+) transients; reduces FT spontaneous Ca(2+) sparks in FT permeabilized myocytes; FT dbSNP:rs121434550). FT {ECO:0000269|PubMed:16908766, FT ECO:0000269|PubMed:17881003, FT ECO:0000269|PubMed:18399795}. FT /FTId=VAR_044118. FT VARIANT 180 180 K -> R (in CPVT2; dbSNP:rs886039816). FT {ECO:0000269|PubMed:27157848}. FT /FTId=VAR_076546. FT VARIANT 244 244 H -> R (in dbSNP:rs28730716). FT /FTId=VAR_067036. FT VARIANT 307 307 D -> H (in CPVT2; reduces calcium- FT binding; impairs calcium-dependent FT oligomerization; causes 50% decrease in FT calcium-dependent binding to TRDN; causes FT 50% decrease in calcium-dependent binding FT to ASPH; dbSNP:rs121434549). FT {ECO:0000269|PubMed:11704930, FT ECO:0000269|PubMed:15485681, FT ECO:0000269|PubMed:17881003}. FT /FTId=VAR_016075. FT VARIANT 335 335 N -> K (in dbSNP:rs28730712). FT /FTId=VAR_067037. FT CONFLICT 67 67 Q -> P (in Ref. 1; BAA23494). FT {ECO:0000305}. FT CONFLICT 175 175 D -> G (in Ref. 2; BAG35873). FT {ECO:0000305}. 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 //