CASQ1_HUMAN
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 03-AUG-2022, entry version 185.
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 (2.02 ANGSTROMS) OF 35-396 IN COMPLEX WITH CALCIUM,
RP 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:27185316, PubMed:26136523). Homodimer (PubMed:27185316,
CC PubMed:26136523, 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";
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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_001231.4.
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 PDBsum; 3UOM; -.
DR PDBsum; 5CRD; -.
DR PDBsum; 5CRE; -.
DR PDBsum; 5CRG; -.
DR PDBsum; 5CRH; -.
DR AlphaFoldDB; P31415; -.
DR SMR; P31415; -.
DR BioGRID; 107294; 5.
DR IntAct; P31415; 3.
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 GlyGen; P31415; 1 site.
DR iPTMnet; P31415; -.
DR PhosphoSitePlus; P31415; -.
DR BioMuta; CASQ1; -.
DR DMDM; 341940551; -.
DR MassIVE; P31415; -.
DR MaxQB; P31415; -.
DR PaxDb; P31415; -.
DR PeptideAtlas; P31415; -.
DR PRIDE; P31415; -.
DR ProteomicsDB; 54788; -.
DR Antibodypedia; 1664; 159 antibodies from 26 providers.
DR DNASU; 844; -.
DR Ensembl; ENST00000368078.8; ENSP00000357057.3; ENSG00000143318.13.
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 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 neXtProt; NX_P31415; -.
DR OpenTargets; ENSG00000143318; -.
DR Orphanet; 2593; Tubular aggregate myopathy.
DR Orphanet; 88635; Vacuolar myopathy with sarcoplasmic reticulum protein aggregates.
DR PharmGKB; PA26095; -.
DR VEuPathDB; HostDB:ENSG00000143318; -.
DR eggNOG; ENOG502QQUJ; Eukaryota.
DR GeneTree; ENSGT00390000019377; -.
DR HOGENOM; CLU_036303_1_0_1; -.
DR InParanoid; P31415; -.
DR OMA; GYPELEY; -.
DR OrthoDB; 1091027at2759; -.
DR PhylomeDB; P31415; -.
DR TreeFam; TF313796; -.
DR PathwayCommons; P31415; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR SignaLink; P31415; -.
DR BioGRID-ORCS; 844; 23 hits in 1072 CRISPR screens.
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 123 other tissues.
DR ExpressionAtlas; P31415; baseline and differential.
DR Genevisible; P31415; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; 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; ISS: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: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:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0007029; P:endoplasmic reticulum organization; IEA:Ensembl.
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:0051279; P:regulation of release of sequestered calcium ion into cytosol; IBA:GO_Central.
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:0009408; P:response to heat; IEA:Ensembl.
DR GO; GO:0010033; P:response to organic substance; 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 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; Calcium; Direct protein sequencing; Disease variant;
KW Endoplasmic reticulum; Glycoprotein; Membrane; Metal-binding;
KW Mitochondrion; Muscle protein; Phosphoprotein; Reference proteome;
KW 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)"
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 store-
FT operated calcium entry (SOCE) activity; 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 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 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 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 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
