ID CASQ1_HUMAN Reviewed; 396 AA. AC P31415; B1AKZ2; B2R863; Q8TBW7; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 04-NOV-2026, entry version 204. DE RecName: Full=Calsequestrin-1; DE AltName: Full=Calmitine {ECO:0000303|PubMed:7945294}; DE AltName: Full=Calsequestrin, skeletal muscle isoform; DE Flags: Precursor; GN Name=CASQ1; Synonyms=CASQ; 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]. RX PubMed=2321095; DOI=10.1007/bf01233048; RA Fujii J., Willard H.F., Maclennan D.H.; RT "Characterization and localization to human chromosome 1 of human fast- RT twitch skeletal muscle calsequestrin gene."; RL Somat. Cell Mol. Genet. 16:185-189(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Skeletal muscle; RX PubMed=7945294; DOI=10.1006/bbrc.1994.2351; RA Bataille N., Schmitt N., Aumercier-Maes P., Ollivier B., Lucas-Heron B., RA Lestienne P.; RT "Molecular cloning of human calmitine, a mitochondrial calcium binding RT protein, reveals identity with calsequestrine."; RL Biochem. Biophys. Res. Commun. 203:1477-1482(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pericardium; 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 [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [7] RP FUNCTION, SUBUNIT, INTERACTION WITH STIM1, AND SUBCELLULAR LOCATION. RX PubMed=27185316; DOI=10.1159/000445574; RA Zhang L., Wang L., Li S., Xue J., Luo D.; RT "Calsequestrin-1 regulates store-operated Ca2+ entry by inhibiting STIM1 RT aggregation."; RL Cell. Physiol. Biochem. 38:2183-2193(2016). RN [8] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH CALCIUM, FUNCTION, AND SUBUNIT. RX PubMed=22337878; DOI=10.1074/jbc.m111.335075; RA Sanchez E.J., Lewis K.M., Danna B.R., Kang C.; RT "High-capacity Ca2+ binding of human skeletal calsequestrin."; RL J. Biol. Chem. 287:11592-11601(2012). RN [9] RP INVOLVEMENT IN VMCQA, VARIANT VMCQA GLY-244, AND CHARACTERIZATION OF RP VARIANT VMCQA GLY-244. RX PubMed=25116801; DOI=10.1002/humu.22631; RA Rossi D., Vezzani B., Galli L., Paolini C., Toniolo L., Pierantozzi E., RA Spinozzi S., Barone V., Pegoraro E., Bello L., Cenacchi G., Vattemi G., RA Tomelleri G., Ricci G., Siciliano G., Protasi F., Reggiani C., RA Sorrentino V.; RT "A mutation in the CASQ1 gene causes a vacuolar myopathy with accumulation RT of sarcoplasmic reticulum protein aggregates."; RL Hum. Mutat. 35:1163-1170(2014). RN [10] RP VARIANT VMCQA GLY-244, CHARACTERIZATION OF VARIANT VMCQA GLY-244, AND RP SUBUNIT. RX PubMed=26136523; DOI=10.1136/jmedgenet-2014-102882; RA Di Blasi C., Sansanelli S., Ruggieri A., Moriggi M., Vasso M., RA D'Adamo A.P., Blasevich F., Zanotti S., Paolini C., Protasi F., Tezzon F., RA Gelfi C., Morandi L., Pessia M., Mora M.; RT "A CASQ1 founder mutation in three Italian families with protein aggregate RT myopathy and hyperCKaemia."; RL J. Med. Genet. 52:617-626(2015). RN [11] RP VARIANT VMCQA GLY-244, CHARACTERIZATION OF VARIANT VMCQA GLY-244, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=27196359; DOI=10.1371/journal.pone.0155516; RA D'Adamo M.C., Sforna L., Visentin S., Grottesi A., Servettini L., RA Guglielmi L., Macchioni L., Saredi S., Curcio M., De Nuccio C., Hasan S., RA Corazzi L., Franciolini F., Mora M., Catacuzzeno L., Pessia M.; RT "A Calsequestrin-1 Mutation Associated with a Skeletal Muscle Disease RT Alters Sarcoplasmic Ca2+ Release."; RL PLoS ONE 11:E0155516-E0155516(2016). RN [12] RP VARIANTS TAM1 ASN-44; ASP-103 AND THR-385, CHARACTERIZATION OF VARIANTS RP TAM1 ASN-44; ASP-103 AND THR-385, CHARACTERIZATION OF VARIANT VMCQA RP GLY-244, INVOLVEMENT IN TAM1, FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=28895244; DOI=10.1002/humu.23338; RA Barone V., Del Re V., Gamberucci A., Polverino V., Galli L., Rossi D., RA Costanzi E., Toniolo L., Berti G., Malandrini A., Ricci G., Siciliano G., RA Vattemi G., Tomelleri G., Pierantozzi E., Spinozzi S., Volpi N., RA Fulceri R., Battistutta R., Reggiani C., Sorrentino V.; RT "Identification and characterization of three novel mutations in the CASQ1 RT gene in four patients with tubular aggregate myopathy."; RL Hum. Mutat. 38:1761-1773(2017). CC -!- FUNCTION: Calsequestrin is a high-capacity, moderate affinity, calcium- CC binding protein and thus acts as an internal calcium store in muscle CC (PubMed:28895244). Calcium ions are bound by clusters of acidic CC residues at the protein surface, often at the interface between CC subunits. Can bind around 80 Ca(2+) ions (PubMed:28895244). Regulates CC the release of lumenal Ca(2+) via the calcium release channel RYR1; CC this plays an important role in triggering muscle contraction. CC Negatively regulates store-operated Ca(2+) entry (SOCE) activity CC (PubMed:27185316). {ECO:0000269|PubMed:22337878, CC ECO:0000269|PubMed:27185316, ECO:0000269|PubMed:28895244, CC ECO:0000303|PubMed:22337878}. CC -!- SUBUNIT: Monomer; increases in response to a depletion of intracellular CC calcium (PubMed:26136523, PubMed:27185316). Homodimer (PubMed:26136523, CC PubMed:27185316, PubMed:28895244). Homotetramer and homopolymer. Can CC form linear homooligomers. Ca(2+) ions promote oligomerization. CC Interacts (via C-terminal end and preferentially with the monomeric CC form) with STIM1; this interaction increases in response to a depletion CC of intracellular calcium, decreases both STIM1 aggregation and CC clustering, interaction of STIM1 with ORAI1 and store-operated Ca(2+) CC entry (SOCE) activity (PubMed:27185316). Interacts with ASPH and TRDN CC (By similarity). {ECO:0000250|UniProtKB:P07221, CC ECO:0000269|PubMed:22337878, ECO:0000269|PubMed:26136523, CC ECO:0000269|PubMed:27185316, ECO:0000269|PubMed:28895244}. CC -!- INTERACTION: CC P31415; Q8NHY3: GAS2L2; NbExp=3; IntAct=EBI-14017981, EBI-7960826; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum CC {ECO:0000269|PubMed:27185316, ECO:0000269|PubMed:28895244}. CC Sarcoplasmic reticulum {ECO:0000269|PubMed:27196359}. Sarcoplasmic CC reticulum lumen {ECO:0000250|UniProtKB:P07221}. Sarcoplasmic reticulum CC membrane; Peripheral membrane protein; Lumenal side CC {ECO:0000250|UniProtKB:P07221}. Mitochondrion matrix CC {ECO:0000250|UniProtKB:O09165}. Note=This isoform of calsequestrin CC occurs in the sarcoplasmic reticulum's terminal cisternae luminal CC spaces of fast skeletal muscle cells. Preferentially forms linear and CC round aggregates in the endoplasmic reticulum (ER) of resting cells CC (PubMed:28895244). In a minority of cells, homogeneously detected in CC the ER lumen (PubMed:28895244). Colocalizes with STIM1 at endoplasmic CC reticulum in response to a depletion of intracellular calcium CC (PubMed:27185316). {ECO:0000250|UniProtKB:P07221, CC ECO:0000269|PubMed:27185316, ECO:0000269|PubMed:28895244}. CC -!- TISSUE SPECIFICITY: Expressed in myoblasts (at protein level). CC {ECO:0000269|PubMed:27196359}. CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P07221}. CC -!- DISEASE: Myopathy, vacuolar, with CASQ1 aggregates (VMCQA) CC [MIM:616231]: An autosomal dominant mild muscle disorder characterized CC by adult onset of muscle cramping and weakness as well as increased CC levels of serum creatine kinase. The disorder is not progressive, and CC some patients may be asymptomatic. {ECO:0000269|PubMed:25116801, CC ECO:0000269|PubMed:26136523, ECO:0000269|PubMed:27196359, CC ECO:0000269|PubMed:28895244}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Myopathy, tubular aggregate, 1 (TAM1) [MIM:160565]: A rare CC congenital myopathy characterized by regular arrays of membrane tubules CC on muscle biopsies without additional histopathological hallmarks. CC Tubular aggregates in muscle are structures of variable appearance CC consisting of an outer tubule containing either one or more CC microtubule-like structures or amorphous material. They may occur in a CC variety of circumstances, including inherited myopathies, alcohol- and CC drug-induced myopathies, exercise-induced cramps or muscle weakness. CC {ECO:0000269|PubMed:28895244}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the calsequestrin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB32063.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH22289.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAG36060.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; S73775; AAB32063.1; ALT_INIT; mRNA. DR EMBL; AK313250; BAG36060.1; ALT_INIT; mRNA. DR EMBL; AL121987; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471121; EAW52736.1; -; Genomic_DNA. DR EMBL; BC022289; AAH22289.1; ALT_INIT; mRNA. DR CCDS; CCDS1198.2; -. DR PIR; A60424; A60424. DR RefSeq; NP_001222.3; NM_001231.5. DR PDB; 3UOM; X-ray; 2.02 A; A/B/C/D/E/F=35-396. DR PDB; 5CRD; X-ray; 2.08 A; A=35-396. DR PDB; 5CRE; X-ray; 3.31 A; A=35-396. DR PDB; 5CRG; X-ray; 1.97 A; A/B/C/D=35-396. DR PDB; 5CRH; X-ray; 2.03 A; A/B=35-396. DR PDB; 8F48; X-ray; 2.90 A; A/B=34-396. DR AlphaFoldDB; P31415; -. DR MDposit; P31415; -. DR SMR; P31415; -. DR BioGRID; 107294; 6. DR FunCoup; P31415; 264. DR IntAct; P31415; 3. DR NDEx; IQUERY-CP-CASQ1; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000357057; -. DR DrugBank; DB11093; Calcium citrate. DR DrugBank; DB13800; Calcium levulinate. DR DrugBank; DB11348; Calcium Phosphate. DR DrugBank; DB14481; Calcium phosphate dihydrate. DR TCDB; 8.A.88.1.1; the calciquestrin (casq) family. DR GlyCosmos; P31415; 1 site, No reported glycans. DR GlyGen; P31415; 1 site. DR iPTMnet; P31415; -. DR PhosphoSitePlus; P31415; -. DR BioMuta; CASQ1; -. DR DMDM; 341940551; -. DR MassIVE; P31415; -. DR PaxDb; 9606-ENSP00000357057; -. DR PeptideAtlas; P31415; -. DR ProteomicsDB; 54788; -. DR Antibodypedia; 1664; 174 antibodies from 31 providers. DR DNASU; 844; -. DR Ensembl; ENST00000368078.8; ENSP00000357057.3; ENSG00000143318.14. DR Ensembl; ENST00000954562.1; ENSP00000624621.1; ENSG00000143318.14. DR GeneID; 844; -. DR KEGG; hsa:844; -. DR MANE-Select; ENST00000368078.8; ENSP00000357057.3; NM_001231.5; NP_001222.3. DR UCSC; uc010pja.3; human. DR AGR; HGNC:1512; -. DR ClinPGx; PA26095; -. DR CTD; 844; -. DR DisGeNET; 844; -. DR GeneCards; CASQ1; -. DR HGNC; HGNC:1512; CASQ1. DR HPA; ENSG00000143318; Group enriched (skeletal muscle, tongue). DR MalaCards; CASQ1; -. DR MIM; 114250; gene. DR MIM; 160565; phenotype. DR MIM; 616231; phenotype. DR OpenTargets; ENSG00000143318; -. DR Orphanet; 2593; Tubular aggregate myopathy. DR Orphanet; 88635; Vacuolar myopathy with sarcoplasmic reticulum protein aggregates. DR VEuPathDB; HostDB:ENSG00000143318; -. DR eggNOG; ENOG502QQUJ; Eukaryota. DR GeneTree; ENSGT00390000019377; -. DR HOGENOM; CLU_036303_1_0_1; -. DR InParanoid; P31415; -. DR OMA; AHLIIAF; -. DR OrthoDB; 10038131at2759; -. DR PAN-GO; P31415; 4 GO annotations based on evolutionary models. DR PhylomeDB; P31415; -. DR PathwayCommons; P31415; -. DR Reactome; R-HSA-2672351; Stimuli-sensing channels. DR Reactome; R-HSA-5578775; Ion homeostasis. DR SignaLink; P31415; -. DR Agora; ENSG00000143318; -. DR BioGRID-ORCS; 844; 23 hits in 1150 CRISPR screens. DR EvolutionaryTrace; P31415; -. DR GenomeRNAi; 844; -. DR Pharos; P31415; Tbio. DR PRO; PR:P31415; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P31415; protein. DR Bgee; ENSG00000143318; Expressed in hindlimb stylopod muscle and 125 other cell types or tissues. DR ExpressionAtlas; P31415; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0014701; C:junctional sarcoplasmic reticulum membrane; IEA:Ensembl. DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; HDA:UniProtKB. DR GO; GO:0016529; C:sarcoplasmic reticulum; EXP:UniProtKB. DR GO; GO:0033018; C:sarcoplasmic reticulum lumen; ISS:UniProtKB. DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0005790; C:smooth endoplasmic reticulum; TAS:ProtInc. DR GO; GO:0030315; C:T-tubule; IEA:Ensembl. DR GO; GO:0014802; C:terminal cisterna; IBA:GO_Central. DR GO; GO:0014804; C:terminal cisterna lumen; IEA:Ensembl. DR GO; GO:0030018; C:Z disc; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0140314; F:calcium ion sequestering activity; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IMP:UniProtKB. DR GO; GO:1901341; P:positive regulation of store-operated calcium channel activity; IMP:UniProtKB. DR GO; GO:0051258; P:protein polymerization; IDA:UniProtKB. DR GO; GO:0014809; P:regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion; ISS:UniProtKB. DR GO; GO:2001256; P:regulation of store-operated calcium entry; IMP:UniProtKB. DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; IEA:Ensembl. DR GO; GO:0045214; P:sarcomere organization; ISS:UniProtKB. DR GO; GO:0007519; P:skeletal muscle tissue development; IEA:Ensembl. 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 FunFam; 3.40.30.10:FF:000031; Calsequestrin; 1. DR FunFam; 3.40.30.10:FF:000033; Calsequestrin; 1. DR FunFam; 3.40.30.10:FF:000047; Calsequestrin; 1. 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:SF14; CALSEQUESTRIN-1; 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. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Direct protein sequencing; Disease variant; KW Endoplasmic reticulum; Glycoprotein; Membrane; Metal-binding; KW Mitochondrion; Muscle protein; Phosphoprotein; Proteomics identification; KW Reference proteome; Sarcoplasmic reticulum; Signal. FT SIGNAL 1..34 FT /evidence="ECO:0000255" FT CHAIN 35..396 FT /note="Calsequestrin-1" FT /id="PRO_0000004212" FT MOD_RES 43 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P19633" FT MOD_RES 81 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19633" FT MOD_RES 124 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P19633" FT MOD_RES 216 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19633" FT CARBOHYD 350 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VARIANT 44 FT /note="D -> N (in TAM1; increased calcium-dependent FT susceptibility to proteolytic degradation; decreased FT calcium-dependent aggregation; decreased calcium-dependent FT polymerization; no effect on subcellular localization; no FT effect on the subcellular localization of STIM1; decreased FT calcium content of intracellular stores; loss of the FT ability to inhibit store-operated calcium entry (SOCE) FT activity; dbSNP:rs140253806)" FT /evidence="ECO:0000269|PubMed:28895244" FT /id="VAR_079704" FT VARIANT 103 FT /note="G -> D (in TAM1; increased calcium-dependent FT susceptibility to proteolytic degradation; decreased FT calcium-dependent aggregation; decreased calcium-dependent FT polymerization; no effect on subcellular localization; no FT effect on the subcellular localization of STIM1; decreased FT calcium content of intracellular stores; no effect of the FT ability to inhibit store-operated calcium entry (SOCE) FT activity; muscle fibers with the mutation have FT significantly decreased calcium-dependent sensitivity to FT caffeine; dbSNP:rs1654108256)" FT /evidence="ECO:0000269|PubMed:28895244" FT /id="VAR_079705" FT VARIANT 140 FT /note="Y -> F (in dbSNP:rs34489853)" FT /id="VAR_053021" FT VARIANT 244 FT /note="D -> G (in VMCQA; no effect on calcium-dependent FT susceptibility to proteolytic degradation; increased FT calcium-dependent aggregation; causes impaired FT polymerization of the protein; no effect on subcellular FT localization; decreased calcium content of sarcoplasmic FT reticulum stores; reduced sarcoplasmic reticulum calcium FT release during excitation-contraction coupling; FT dbSNP:rs730882052)" FT /evidence="ECO:0000269|PubMed:25116801, FT ECO:0000269|PubMed:26136523, ECO:0000269|PubMed:27196359, FT ECO:0000269|PubMed:28895244" FT /id="VAR_073337" FT VARIANT 385 FT /note="I -> T (in TAM1; no effect on calcium-dependent FT susceptibility to proteolytic degradation; increased FT moderately calcium-dependent aggregation; increased FT moderately calcium-dependent polymerization; no effect on FT subcellular localization; no effect on the subcellular FT localization of STIM1; decreased calcium content of FT intracellular stores; loss of the ability to inhibit FT store-operated calcium entry (SOCE) activity; FT dbSNP:rs371278891)" FT /evidence="ECO:0000269|PubMed:28895244" FT /id="VAR_079706" FT CONFLICT 356..357 FT /note="SV -> RL (in Ref. 2; AAB32063)" FT /evidence="ECO:0000305" FT HELIX 37..41 FT /evidence="ECO:0007829|PDB:5CRD" FT STRAND 49..51 FT /evidence="ECO:0007829|PDB:3UOM" FT TURN 54..56 FT /evidence="ECO:0007829|PDB:5CRG" FT HELIX 57..63 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 65..72 FT /evidence="ECO:0007829|PDB:5CRG" FT HELIX 73..76 FT /evidence="ECO:0007829|PDB:5CRG" FT HELIX 79..98 FT /evidence="ECO:0007829|PDB:5CRG" FT TURN 99..103 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 104..110 FT /evidence="ECO:0007829|PDB:5CRG" FT TURN 111..114 FT /evidence="ECO:0007829|PDB:5CRG" FT HELIX 115..121 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 129..133 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 136..140 FT /evidence="ECO:0007829|PDB:5CRG" FT HELIX 146..157 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 160..163 FT /evidence="ECO:0007829|PDB:5CRG" FT HELIX 167..175 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 181..185 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 189..191 FT /evidence="ECO:0007829|PDB:5CRE" FT HELIX 192..204 FT /evidence="ECO:0007829|PDB:5CRG" FT TURN 205..207 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 210..213 FT /evidence="ECO:0007829|PDB:5CRG" FT HELIX 216..222 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 229..232 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 240..242 FT /evidence="ECO:0007829|PDB:8F48" FT STRAND 243..246 FT /evidence="ECO:0007829|PDB:5CRG" FT HELIX 249..258 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 263..266 FT /evidence="ECO:0007829|PDB:5CRG" FT HELIX 269..271 FT /evidence="ECO:0007829|PDB:5CRG" FT HELIX 272..276 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 283..288 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 291..293 FT /evidence="ECO:0007829|PDB:5CRE" FT HELIX 294..309 FT /evidence="ECO:0007829|PDB:5CRG" FT TURN 310..312 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 318..321 FT /evidence="ECO:0007829|PDB:5CRG" FT HELIX 323..325 FT /evidence="ECO:0007829|PDB:5CRG" FT HELIX 327..329 FT /evidence="ECO:0007829|PDB:5CRG" FT HELIX 330..337 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 341..343 FT /evidence="ECO:0007829|PDB:5CRE" FT STRAND 345..350 FT /evidence="ECO:0007829|PDB:5CRG" FT TURN 351..353 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 356..358 FT /evidence="ECO:0007829|PDB:5CRG" FT STRAND 363..365 FT /evidence="ECO:0007829|PDB:5CRE" FT HELIX 366..369 FT /evidence="ECO:0007829|PDB:3UOM" FT HELIX 370..381 FT /evidence="ECO:0007829|PDB:5CRG" SQ SEQUENCE 396 AA; 45160 MW; C20388AD8870E12D CRC64; MSATDRMGPR AVPGLRLALL LLLVLGTPKS GVQGQEGLDF PEYDGVDRVI NVNAKNYKNV FKKYEVLALL YHEPPEDDKA SQRQFEMEEL ILELAAQVLE DKGVGFGLVD SEKDAAVAKK LGLTEVDSMY VFKGDEVIEY DGEFSADTIV EFLLDVLEDP VELIEGEREL QAFENIEDEI KLIGYFKSKD SEHYKAFEDA AEEFHPYIPF FATFDSKVAK KLTLKLNEID FYEAFMEEPV TIPDKPNSEE EIVNFVEEHR RSTLRKLKPE SMYETWEDDM DGIHIVAFAE EADPDGFEFL ETLKAVAQDN TENPDLSIIW IDPDDFPLLV PYWEKTFDID LSAPQIGVVN VTDADSVWME MDDEEDLPSA EELEDWLEDV LEGEINTEDD DDDDDD //