Protein: Calsequestrin-1 (Calmitine) (Calsequestrin, skeletal muscle isoform) (P31415)
Organism: Homo sapiens (Human)
Function: Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. Calcium ions are bound by clusters of acidic residues at the protein surface, often at the interface between subunits. Can bind around 80 Ca(2+) ions. Regulates the release of lumenal Ca(2+) via the calcium release channel RYR1; this plays an important role in triggering muscle contraction. Negatively regulates store-operated Ca(2+) entry (SOCE) activity.
Subcellular location: Endoplasmic reticulum {ECO:0000269|PubMed:27185316, ECO:0000269|PubMed:28895244}. Sarcoplasmic reticulum {ECO:0000269|PubMed:27196359}. Sarcoplasmic reticulum lumen {ECO:0000250|UniProtKB:P07221}. Sarcoplasmic reticulum membrane; Peripheral membrane protein; Lumenal side {ECO:0000250|UniProtKB:P07221}. Mitochondrion matrix {ECO:0000250|UniProtKB:O09165}. Note=This isoform of calsequestrin occurs in the sarcoplasmic reticulum's terminal cisternae luminal spaces of fast skeletal muscle cells. Preferentially forms linear and round aggregates in the endoplasmic reticulum (ER) of resting cells (PubMed:28895244). In a minority of cells, homogeneously detected in the ER lumen (PubMed:28895244). Colocalizes with STIM1 at endoplasmic reticulum in response to a depletion of intracellular calcium (PubMed:27185316). {ECO:0000250|UniProtKB:P07221, ECO:0000269|PubMed:27185316, ECO:0000269|PubMed:28895244}.
Sequence: MSATDRMGPRAVPGLRLALLLLLVLGTPKSGVQGQEGLDFPEYDGVDRVINVNAKNYKNVFKKYEVLALLYHEPPEDDKASQRQFEMEELILELAAQVLEDKGVGFGLVDSEKDAAVAKKLGLTEVDSMYVFKGDEVIEYDGEFSADTIVEFLLDVLEDPVELIEGERELQAFENIEDEIKLIGYFKSKDSEHYKAFEDAAEEFHPYIPFFATFDSKVAKKLTLKLNEIDFYEAFMEEPVTIPDKPNSEEEIVNFVEEHRRSTLRKLKPESMYETWEDDMDGIHIVAFAEEADPDGFEFLETLKAVAQDNTENPDLSIIWIDPDDFPLLVPYWEKTFDIDLSAPQIGVVNVTDADSVWMEMDDEEDLPSAEELEDWLEDVLEGEINTEDDDDDDDD
InterPro domains: - IPR036249: Thioredoxin-like superfamily (homologous_superfamily) [39-381]
- IPR001393: Calsequestrin (family) [12-396]
- IPR041858: Calsequestrin, middle TRX-fold domain (domain) [160-261]
- IPR041859: Calsequestrin, N-terminal TRX-fold domain (domain) [39-158]
- IPR041860: Calsequestrin, C-terminal TRX-fold domain (domain) [262-381]
- IPR018233: Calsequestrin, conserved site (conserved_site) [35-391]
Interaction partners: - Aspartyl/asparaginyl beta-hydroxylase
- Triadin
- Ryanodine receptor 1
- Ryanodine receptor 2
- Ryanodine receptor 3
- Calsequestrin-2
- Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
- Myosin light chain 1/3, skeletal muscle isoform
- Sarcalumenin
- Junctional sarcoplasmic reticulum protein 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0043167 (ion binding), GO:0005515 (protein binding), GO:0042802 (identical protein binding), GO:0043169 (cation binding), GO:0046983 (protein dimerization activity), GO:0042803 (protein homodimerization activity), GO:0046872 (metal ion binding), GO:0005509 (calcium ion binding)
Biological Process (BP): GO:0008150 (biological process), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0042592 (homeostatic process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0051641 (cellular localization), GO:0051651 (maintenance of location in cell), GO:0051051 (negative regulation of transport), GO:0042221 (response to chemical), GO:0032879 (regulation of localization), GO:0071840 (cellular component organization or biogenesis), GO:0051239 (regulation of multicellular organismal process), GO:0003008 (system process), GO:0048878 (chemical homeostasis), GO:0065008 (regulation of biological quality), GO:0019725 (cellular homeostasis), GO:0009719 (response to endogenous stimulus), GO:0040017 (positive regulation of locomotion), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0030029 (actin filament-based process), GO:0048523 (negative regulation of cellular process), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0040012 (regulation of locomotion), GO:0048522 (positive regulation of cellular process), GO:0050801 (monoatomic ion homeostasis), GO:0051049 (regulation of transport), GO:2000145 (regulation of cell motility), GO:0051282 (regulation of sequestering of calcium ion), GO:0032409 (regulation of transporter activity), GO:0044092 (negative regulation of molecular function), GO:0044057 (regulation of system process), GO:0034762 (regulation of transmembrane transport), GO:0071495 (cellular response to endogenous stimulus), GO:0098771 (inorganic ion homeostasis), GO:1901700 (response to oxygen-containing compound), GO:0003013 (circulatory system process), GO:0010033 (response to organic substance), GO:0009725 (response to hormone), GO:2000147 (positive regulation of cell motility), GO:0034763 (negative regulation of transmembrane transport), GO:0003012 (muscle system process), GO:0055082 (intracellular chemical homeostasis), GO:0010035 (response to inorganic substance), GO:0002027 (regulation of heart rate), GO:1901698 (response to nitrogen compound), GO:0032410 (negative regulation of transporter activity), GO:0010646 (regulation of cell communication), GO:0070887 (cellular response to chemical stimulus), GO:0043271 (negative regulation of monoatomic ion transport), GO:0051238 (sequestering of metal ion), GO:0016043 (cellular component organization), GO:0051284 (positive regulation of sequestering of calcium ion), GO:1902074 (response to salt), GO:0010038 (response to metal ion), GO:0071417 (cellular response to organonitrogen compound), GO:0010649 (regulation of cell communication by electrical coupling), GO:0008015 (blood circulation), GO:0071310 (cellular response to organic substance), GO:0034765 (regulation of monoatomic ion transmembrane transport), GO:0006936 (muscle contraction), GO:1901699 (cellular response to nitrogen compound), GO:0090257 (regulation of muscle system process), GO:0030334 (regulation of cell migration), GO:0006873 (intracellular monoatomic ion homeostasis), GO:1903522 (regulation of blood circulation), GO:0055074 (calcium ion homeostasis), GO:1903115 (regulation of actin filament-based movement), GO:0019932 (second-messenger-mediated signaling), GO:0032413 (negative regulation of ion transmembrane transporter activity), GO:0051592 (response to calcium ion), GO:0010243 (response to organonitrogen compound), GO:0034766 (negative regulation of monoatomic ion transmembrane transport), GO:0055080 (monoatomic cation homeostasis), GO:0003015 (heart process), GO:0070252 (actin-mediated cell contraction), GO:0051926 (negative regulation of calcium ion transport), GO:0022898 (regulation of transmembrane transporter activity), GO:0014070 (response to organic cyclic compound), GO:0043269 (regulation of monoatomic ion transport), GO:0006996 (organelle organization), GO:0031032 (actomyosin structure organization), GO:1901701 (cellular response to oxygen-containing compound), GO:0097435 (supramolecular fiber organization), GO:0051279 (regulation of release of sequestered calcium ion into cytosol), GO:0071415 (cellular response to purine-containing compound), GO:0006937 (regulation of muscle contraction), GO:0010880 (regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum), GO:1901020 (negative regulation of calcium ion transmembrane transporter activity), GO:0043279 (response to alkaloid), GO:0060047 (heart contraction), GO:1904064 (positive regulation of cation transmembrane transport), GO:0032412 (regulation of monoatomic ion transmembrane transporter activity), GO:1904063 (negative regulation of cation transmembrane transport), GO:0010959 (regulation of metal ion transport), GO:0019722 (calcium-mediated signaling), GO:0071407 (cellular response to organic cyclic compound), GO:0030003 (intracellular monoatomic cation homeostasis), GO:0007010 (cytoskeleton organization), GO:0006941 (striated muscle contraction), GO:0008016 (regulation of heart contraction), GO:0071312 (cellular response to alkaloid), GO:2001258 (negative regulation of cation channel activity), GO:1903170 (negative regulation of calcium ion transmembrane transport), GO:1904062 (regulation of monoatomic cation transmembrane transport), GO:0006874 (intracellular calcium ion homeostasis), GO:0014074 (response to purine-containing compound), GO:0060314 (regulation of ryanodine-sensitive calcium-release channel activity), GO:0010881 (regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion), GO:0055117 (regulation of cardiac muscle contraction), GO:2001257 (regulation of cation channel activity), GO:0006942 (regulation of striated muscle contraction), GO:0060048 (cardiac muscle contraction), GO:0031000 (response to caffeine), GO:0071313 (cellular response to caffeine), GO:0051924 (regulation of calcium ion transport), GO:0010882 (regulation of cardiac muscle contraction by calcium ion signaling), GO:1901019 (regulation of calcium ion transmembrane transporter activity), GO:1903169 (regulation of calcium ion transmembrane transport)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031974 (membrane-enclosed lumen), GO:0009986 (cell surface), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0043233 (organelle lumen), GO:0005783 (endoplasmic reticulum), GO:0043229 (intracellular organelle), GO:0016528 (sarcoplasm), GO:0043227 (membrane-bounded organelle), GO:0043228 (non-membrane-bounded organelle), GO:0016529 (sarcoplasmic reticulum), GO:0005788 (endoplasmic reticulum lumen), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0005856 (cytoskeleton)