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Protein

Calsequestrin-1

Gene

CASQ1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle (PubMed:28895244). Calcium ions are bound by clusters of acidic residues at the protein surface, often at the interface between subunits. Can bind around 80 Ca2+ ions (PubMed:28895244). Regulates the release of lumenal Ca2+ via the calcium release channel RYR1; this plays an important role in triggering muscle contraction. Negatively regulates store-operated Ca2+ entry (SOCE) activity (PubMed:27185316).1 Publication3 Publications

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • identical protein binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionMuscle protein
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels
R-HSA-5578775 Ion homeostasis

Protein family/group databases

TCDBi8.A.88.1.1 the calciquestrin (casq) family

Names & Taxonomyi

Protein namesi
Recommended name:
Calsequestrin-1
Alternative name(s):
Calmitine1 Publication
Calsequestrin, skeletal muscle isoform
Gene namesi
Name:CASQ1
Synonyms:CASQ
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000143318.12
HGNCiHGNC:1512 CASQ1
MIMi114250 gene
neXtProtiNX_P31415

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Mitochondrion, Sarcoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Myopathy, vacuolar, with CASQ1 aggregates (VMCQA)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant mild muscle disorder characterized by adult onset of muscle cramping and weakness as well as increased levels of serum creatine kinase. The disorder is not progressive, and some patients may be asymptomatic.
See also OMIM:616231
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073337244D → G in VMCQA; no effect on calcium-dependent susceptibility to proteolytic degradation; increased calcium-dependent aggregation; causes impaired polymerization of the protein; no effect on subcellular localization; decreased calcium content of sarcoplasmic reticulum stores; reduced sarcoplasmic reticulum calcium release during excitation-contraction coupling. 4 PublicationsCorresponds to variant dbSNP:rs730882052EnsemblClinVar.1
Myopathy, tubular aggregate, 1 (TAM1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare congenital myopathy characterized by regular arrays of membrane tubules on muscle biopsies without additional histopathological hallmarks. Tubular aggregates in muscle are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. They may occur in a variety of circumstances, including inherited myopathies, alcohol- and drug-induced myopathies, exercise-induced cramps or muscle weakness.
See also OMIM:160565
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07970444D → N in TAM1; increased calcium-dependent susceptibility to proteolytic degradation; decreased calcium-dependent aggregation; decreased calcium-dependent polymerization; no effect on subcellular localization; no effect on the subcellular localization of STIM1; decreased calcium content of intracellular stores; loss of the ability to inhibit store-operated calcium entry (SOCE) activity. 1 PublicationCorresponds to variant dbSNP:rs140253806Ensembl.1
Natural variantiVAR_079705103G → D in TAM1; increased calcium-dependent susceptibility to proteolytic degradation; decreased calcium-dependent aggregation; decreased calcium-dependent polymerization; no effect on subcellular localization; no effect on the subcellular localization of STIM1; decreased calcium content of intracellular stores; no effect of the ability to inhibit store-operated calcium entry (SOCE) activity; muscle fibers with the mutation have significantly decreased calcium-dependent sensitivity to caffeine. 1 Publication1
Natural variantiVAR_079706385I → T in TAM1; no effect on calcium-dependent susceptibility to proteolytic degradation; increased moderately calcium-dependent aggregation; increased moderately calcium-dependent polymerization; no effect on subcellular localization; no effect on the subcellular localization of STIM1; decreased calcium content of intracellular stores; loss of the ability to inhibit store-operated calcium entry (SOCE) activity. 1 PublicationCorresponds to variant dbSNP:rs371278891Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi844
MalaCardsiCASQ1
MIMi160565 phenotype
616231 phenotype
OpenTargetsiENSG00000143318
Orphaneti88635 Myopathy due to calsequestrin and SERCA1 protein overload
PharmGKBiPA26095

Polymorphism and mutation databases

BioMutaiCASQ1
DMDMi341940551

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 34Sequence analysisAdd BLAST34
ChainiPRO_000000421235 – 396Calsequestrin-1Add BLAST362

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei43PhosphotyrosineBy similarity1
Modified residuei81PhosphoserineBy similarity1
Modified residuei124PhosphothreonineBy similarity1
Modified residuei216PhosphoserineBy similarity1
Glycosylationi350N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP31415
PaxDbiP31415
PeptideAtlasiP31415
PRIDEiP31415
ProteomicsDBi54788

PTM databases

iPTMnetiP31415
PhosphoSitePlusiP31415

Expressioni

Tissue specificityi

Expressed in myoblasts (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000143318
CleanExiHS_CASQ1
ExpressionAtlasiP31415 baseline and differential
GenevisibleiP31415 HS

Organism-specific databases

HPAiCAB015170
HPA007845
HPA026823

Interactioni

Subunit structurei

Monomer; increases in response to a depletion of intracellular calcium (PubMed:27185316, PubMed:26136523). Homodimer (PubMed:27185316, PubMed:26136523, PubMed:28895244). homotetramer and homopolymer. Can form linear homooligomers. Ca2+ ions promote oligomerization. Interacts (via C-terminal end and preferentially with the monomeric form) with STIM1; this interaction increases in response to a depletion of intracellular calcium, decreases both STIM1 aggregation and clustering, interaction of STIM1 with ORAI1 and store-operated Ca2+ entry (SOCE) activity (PubMed:27185316). Interacts with ASPH and TRDN (By similarity).By similarity4 Publications

GO - Molecular functioni

  • identical protein binding Source: UniProtKB

Protein-protein interaction databases

IntActiP31415, 1 interactor
STRINGi9606.ENSP00000357057

Structurei

Secondary structure

1396
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi49 – 51Combined sources3
Turni54 – 56Combined sources3
Helixi57 – 63Combined sources7
Beta strandi65 – 72Combined sources8
Helixi79 – 98Combined sources20
Turni99 – 103Combined sources5
Beta strandi104 – 110Combined sources7
Turni111 – 114Combined sources4
Helixi115 – 121Combined sources7
Beta strandi129 – 133Combined sources5
Beta strandi136 – 140Combined sources5
Helixi146 – 157Combined sources12
Beta strandi160 – 163Combined sources4
Helixi167 – 175Combined sources9
Beta strandi181 – 185Combined sources5
Beta strandi189 – 191Combined sources3
Helixi192 – 204Combined sources13
Turni205 – 207Combined sources3
Beta strandi210 – 213Combined sources4
Helixi216 – 222Combined sources7
Beta strandi229 – 232Combined sources4
Beta strandi243 – 246Combined sources4
Helixi249 – 258Combined sources10
Beta strandi263 – 266Combined sources4
Helixi269 – 271Combined sources3
Helixi272 – 276Combined sources5
Beta strandi283 – 288Combined sources6
Beta strandi291 – 293Combined sources3
Helixi294 – 309Combined sources16
Turni310 – 312Combined sources3
Beta strandi318 – 321Combined sources4
Helixi323 – 325Combined sources3
Helixi327 – 329Combined sources3
Helixi330 – 337Combined sources8
Beta strandi341 – 343Combined sources3
Beta strandi345 – 350Combined sources6
Turni351 – 353Combined sources3
Beta strandi356 – 358Combined sources3
Beta strandi363 – 365Combined sources3
Helixi370 – 381Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3UOMX-ray2.02A/B/C/D/E/F35-396[»]
5CRDX-ray2.08A35-396[»]
5CREX-ray3.31A35-396[»]
5CRGX-ray1.97A/B/C/D35-396[»]
5CRHX-ray2.03A/B35-396[»]
ProteinModelPortaliP31415
SMRiP31415
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi15 – 25Poly-LeuAdd BLAST11
Compositional biasi353 – 396Asp-richAdd BLAST44

Sequence similaritiesi

Belongs to the calsequestrin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IGY5 Eukaryota
ENOG4111R2M LUCA
GeneTreeiENSGT00390000019377
HOGENOMiHOG000049047
HOVERGENiHBG050805
InParanoidiP31415
OMAiSGVQGEE
OrthoDBiEOG091G08VX
PhylomeDBiP31415
TreeFamiTF313796

Family and domain databases

InterProiView protein in InterPro
IPR001393 Calsequestrin
IPR018233 Calsequestrin_CS
IPR036249 Thioredoxin-like_sf
PANTHERiPTHR10033 PTHR10033, 1 hit
PfamiView protein in Pfam
PF01216 Calsequestrin, 1 hit
SUPFAMiSSF52833 SSF52833, 3 hits
PROSITEiView protein in PROSITE
PS00863 CALSEQUESTRIN_1, 1 hit
PS00864 CALSEQUESTRIN_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P31415-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSATDRMGPR AVPGLRLALL LLLVLGTPKS GVQGQEGLDF PEYDGVDRVI
60 70 80 90 100
NVNAKNYKNV FKKYEVLALL YHEPPEDDKA SQRQFEMEEL ILELAAQVLE
110 120 130 140 150
DKGVGFGLVD SEKDAAVAKK LGLTEVDSMY VFKGDEVIEY DGEFSADTIV
160 170 180 190 200
EFLLDVLEDP VELIEGEREL QAFENIEDEI KLIGYFKSKD SEHYKAFEDA
210 220 230 240 250
AEEFHPYIPF FATFDSKVAK KLTLKLNEID FYEAFMEEPV TIPDKPNSEE
260 270 280 290 300
EIVNFVEEHR RSTLRKLKPE SMYETWEDDM DGIHIVAFAE EADPDGFEFL
310 320 330 340 350
ETLKAVAQDN TENPDLSIIW IDPDDFPLLV PYWEKTFDID LSAPQIGVVN
360 370 380 390
VTDADSVWME MDDEEDLPSA EELEDWLEDV LEGEINTEDD DDDDDD
Length:396
Mass (Da):45,160
Last modified:July 27, 2011 - v3
Checksum:iC20388AD8870E12D
GO

Sequence cautioni

The sequence AAB32063 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH22289 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAG36060 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti356 – 357SV → RL in AAB32063 (PubMed:7945294).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07970444D → N in TAM1; increased calcium-dependent susceptibility to proteolytic degradation; decreased calcium-dependent aggregation; decreased calcium-dependent polymerization; no effect on subcellular localization; no effect on the subcellular localization of STIM1; decreased calcium content of intracellular stores; loss of the ability to inhibit store-operated calcium entry (SOCE) activity. 1 PublicationCorresponds to variant dbSNP:rs140253806Ensembl.1
Natural variantiVAR_079705103G → D in TAM1; increased calcium-dependent susceptibility to proteolytic degradation; decreased calcium-dependent aggregation; decreased calcium-dependent polymerization; no effect on subcellular localization; no effect on the subcellular localization of STIM1; decreased calcium content of intracellular stores; no effect of the ability to inhibit store-operated calcium entry (SOCE) activity; muscle fibers with the mutation have significantly decreased calcium-dependent sensitivity to caffeine. 1 Publication1
Natural variantiVAR_053021140Y → F. Corresponds to variant dbSNP:rs34489853Ensembl.1
Natural variantiVAR_073337244D → G in VMCQA; no effect on calcium-dependent susceptibility to proteolytic degradation; increased calcium-dependent aggregation; causes impaired polymerization of the protein; no effect on subcellular localization; decreased calcium content of sarcoplasmic reticulum stores; reduced sarcoplasmic reticulum calcium release during excitation-contraction coupling. 4 PublicationsCorresponds to variant dbSNP:rs730882052EnsemblClinVar.1
Natural variantiVAR_079706385I → T in TAM1; no effect on calcium-dependent susceptibility to proteolytic degradation; increased moderately calcium-dependent aggregation; increased moderately calcium-dependent polymerization; no effect on subcellular localization; no effect on the subcellular localization of STIM1; decreased calcium content of intracellular stores; loss of the ability to inhibit store-operated calcium entry (SOCE) activity. 1 PublicationCorresponds to variant dbSNP:rs371278891Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S73775 mRNA Translation: AAB32063.1 Different initiation.
AK313250 mRNA Translation: BAG36060.1 Different initiation.
AL121987 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW52736.1
BC022289 mRNA Translation: AAH22289.1 Different initiation.
CCDSiCCDS1198.2
PIRiA60424
RefSeqiNP_001222.3, NM_001231.4
UniGeneiHs.632476

Genome annotation databases

EnsembliENST00000368078; ENSP00000357057; ENSG00000143318
GeneIDi844
KEGGihsa:844
UCSCiuc010pja.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCASQ1_HUMAN
AccessioniPrimary (citable) accession number: P31415
Secondary accession number(s): B1AKZ2, B2R863, Q8TBW7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 27, 2011
Last modified: June 20, 2018
This is version 160 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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