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O14958 (CASQ2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calsequestrin-2
Alternative name(s):
Calsequestrin, cardiac muscle isoform
Gene names
Name:CASQ2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length399 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. The release of calcium bound to calsequestrin through a calcium release channel triggers muscle contraction. The skeletal muscle isoform (CASQ1)binds around 80 Ca2+ ions, while the cardiac isoform (CASQ2)binds approximately 60 Ca2+ ions. Ref.8

Subunit structure

Monomer, homodimer and homooligomer. Mostly monomeric in the absence of calcium. Forms higher oligomers in a calcium-dependent manner. Dimers associate to form tetramers, that then form linear homopolymer chains. Ref.8

Subcellular location

Sarcoplasmic reticulum lumen. Note: This isoform ofcalsequestrin occurs in the sarcoplasmic reticulum's terminal cisternae luminal spaces of cardiac and slow skeletal muscle cells.

Post-translational modification

Phosphorylation in the C-terminus, probably by CK2, moderately increases calcium buffering capacity.

Involvement in disease

Ventricular tachycardia, catecholaminergic polymorphic, 2 (CPVT2) [MIM:611938]: An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, seizures, or sudden death after physical activity or emotional stress.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.11 Ref.12 Ref.13

Sequence similarities

Belongs to the calsequestrin family.

Ontologies

Keywords
   Cellular componentSarcoplasmic reticulum
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainSignal
   LigandCalcium
   Molecular functionMuscle protein
   PTMGlycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processPurkinje myocyte to ventricular cardiac muscle cell signaling

Non-traceable author statement PubMed 22198169. Source: BHF-UCL

cardiac muscle contraction

Inferred from mutant phenotype Ref.12. Source: BHF-UCL

cellular response to caffeine

Inferred from mutant phenotype Ref.12. Source: BHF-UCL

detection of calcium ion

Traceable author statement PubMed 22123818. Source: BHF-UCL

ion transmembrane transport

Traceable author statement. Source: Reactome

negative regulation of potassium ion transmembrane transporter activity

Inferred from sequence or structural similarity PubMed 21063088. Source: BHF-UCL

negative regulation of potassium ion transport

Inferred from sequence or structural similarity PubMed 21063088. Source: BHF-UCL

negative regulation of ryanodine-sensitive calcium-release channel activity

Inferred from direct assay PubMed 16601229. Source: BHF-UCL

protein polymerization

Inferred from direct assay PubMed 22123818. Source: BHF-UCL

regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion

Inferred from mutant phenotype PubMed 16601229Ref.12. Source: BHF-UCL

regulation of cell communication by electrical coupling

Inferred from mutant phenotype Ref.12. Source: BHF-UCL

regulation of heart rate

Inferred from mutant phenotype PubMed 16601229Ref.12. Source: BHF-UCL

regulation of membrane repolarization

Inferred from sequence or structural similarity PubMed 21063088. Source: BHF-UCL

regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum

Inferred from sequence or structural similarity. Source: BHF-UCL

sequestering of calcium ion

Inferred from direct assay PubMed 16601229. Source: BHF-UCL

striated muscle contraction

Traceable author statement PubMed 9795116. Source: ProtInc

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentZ disc

Inferred from sequence or structural similarity. Source: BHF-UCL

calcium channel complex

Traceable author statement PubMed 19403607. Source: BHF-UCL

cytoplasm

Inferred from direct assay PubMed 22123818. Source: BHF-UCL

intracellular

Inferred from mutant phenotype Ref.12. Source: BHF-UCL

junctional sarcoplasmic reticulum membrane

Traceable author statement PubMed 17569730. Source: BHF-UCL

sarcoplasmic reticulum

Inferred from sequence or structural similarity. Source: BHF-UCL

sarcoplasmic reticulum lumen

Inferred by curator Ref.12. Source: BHF-UCL

sarcoplasmic reticulum membrane

Traceable author statement. Source: Reactome

   Molecular_functioncalcium ion binding

Inferred from direct assay PubMed 16601229Ref.12. Source: BHF-UCL

protein homodimerization activity

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 By similarity
Chain20 – 399380Calsequestrin-2
PRO_0000004218

Regions

Compositional bias356 – 39944Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue3851Phosphoserine Ref.7
Modified residue3931Phosphoserine Ref.7
Glycosylation3351N-linked (GlcNAc...) Potential

Natural variations

Natural variant331R → Q in CPVT2; reduces calcium-dependent dimerization. Ref.8 Ref.13
VAR_055234
Natural variant661T → A. Ref.8 Ref.10
Corresponds to variant rs4074536 [ dbSNP | Ensembl ].
VAR_023692
Natural variant761V → M. Ref.8 Ref.10
Corresponds to variant rs10801999 [ dbSNP | Ensembl ].
VAR_023693
Natural variant1671L → H in CPVT2; alters protein folding, reduces calcium-binding and calcium-dependent oligomerization, decreases sarcoplasmic reticulum Ca(2+) storing capacity and reduces the amplitude of I(Ca)-induced Ca(2+) transients and of spontaneous Ca(2+) sparks in permeabilized myocytes. Ref.8 Ref.12 Ref.13
VAR_044118
Natural variant2441H → R.
Corresponds to variant rs28730716 [ dbSNP | Ensembl ].
VAR_067036
Natural variant3071D → H in CPVT2; reduces calcium-binding and causes 50% decrease in calcium-dependent binding to triadin-1 and junctin. Ref.8 Ref.9 Ref.11
VAR_016075
Natural variant3351N → K.
Corresponds to variant rs28730712 [ dbSNP | Ensembl ].
VAR_067037

Experimental info

Sequence conflict671Q → P in BAA23494. Ref.1
Sequence conflict1751D → G in BAG35873. Ref.2

Secondary structure

....................................... 399
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O14958 [UniParc].

Last modified September 19, 2002. Version 2.
Checksum: 7794DC2FF7E4B064

FASTA39946,436
        10         20         30         40         50         60 
MKRTHLFIVG IYFLSSCRAE EGLNFPTYDG KDRVVSLSEK NFKQVLKKYD LLCLYYHEPV 

        70         80         90        100        110        120 
SSDKVTQKQF QLKEIVLELV AQVLEHKAIG FVMVDAKKEA KLAKKLGFDE EGSLYILKGD 

       130        140        150        160        170        180 
RTIEFDGEFA ADVLVEFLLD LIEDPVEIIS SKLEVQAFER IEDYIKLIGF FKSEDSEYYK 

       190        200        210        220        230        240 
AFEEAAEHFQ PYIKFFATFD KGVAKKLSLK MNEVDFYEPF MDEPIAIPNK PYTEEELVEF 

       250        260        270        280        290        300 
VKEHQRPTLR RLRPEEMFET WEDDLNGIHI VAFAEKSDPD GYEFLEILKQ VARDNTDNPD 

       310        320        330        340        350        360 
LSILWIDPDD FPLLVAYWEK TFKIDLFRPQ IGVVNVTDAD SVWMEIPDDD DLPTAEELED 

       370        380        390 
WIEDVLSGKI NTEDDDEDDD DDDNSDEEDN DDSDDDDDE 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of a human cDNA for cardiac calsequestrin and its chromosomal assignment to 1p13.3 by fluorescence in situ hybridization."
Tanaka T., Inazawa J., Nakamura Y.
Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skeletal muscle.
[6]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"Phosphorylation of human calsequestrin: implications for calcium regulation."
Sanchez E.J., Munske G.R., Criswell A., Milting H., Dunker A.K., Kang C.
Mol. Cell. Biochem. 353:195-204(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-385 AND SER-393.
[8]"Characterization of human cardiac calsequestrin and its deleterious mutants."
Kim E., Youn B., Kemper L., Campbell C., Milting H., Varsanyi M., Kang C.
J. Mol. Biol. 373:1047-1057(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) OF 22-399, SUBUNIT, FUNCTION, CHARACTERIZATION OF VARIANTS CPVT2 GLN-33; HIS-167 AND HIS-307, CHARACTERIZATION OF VARIANTS ALA-66 AND MET-76.
[9]"A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel."
Lahat H., Pras E., Olender T., Avidan N., Ben-Asher E., Man O., Levy-Nissenbaum E., Khoury A., Lorber A., Goldman B., Lancet D., Eldar M.
Am. J. Hum. Genet. 69:1378-1384(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPVT2 HIS-307.
[10]"Molecular genetics of exercise-induced polymorphic ventricular tachycardia: identification of three novel cardiac ryanodine receptor mutations and two common calsequestrin 2 amino-acid polymorphisms."
Laitinen P.J., Swan H., Kontula K.
Eur. J. Hum. Genet. 11:888-891(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-66 AND MET-76.
[11]"Calsequestrin mutant D307H exhibits depressed binding to its protein targets and a depressed response to calcium."
Houle T.D., Ram M.L., Cala S.E.
Cardiovasc. Res. 64:227-233(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT CPVT2 HIS-307.
[12]"Clinical phenotype and functional characterization of CASQ2 mutations associated with catecholaminergic polymorphic ventricular tachycardia."
di Barletta M.R., Viatchenko-Karpinski S., Nori A., Memmi M., Terentyev D., Turcato F., Valle G., Rizzi N., Napolitano C., Gyorke S., Volpe P., Priori S.G.
Circulation 114:1012-1019(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPVT2 HIS-167, CHARACTERIZATION OF VARIANT CPVT2 HIS-167.
[13]"Catecholaminergic polymorphic ventricular tachycardia-related mutations R33Q and L167H alter calcium sensitivity of human cardiac calsequestrin."
Valle G., Galla D., Nori A., Priori S.G., Gyorke S., de Filippis V., Volpe P.
Biochem. J. 413:291-303(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CPVT2 GLN-33 AND HIS-167, CHARACTERIZATION OF VARIANTS CPVT2 GLN-33 AND HIS-167.
+Additional computationally mapped references.

Web resources

GeneReviews
Wikipedia

Calsequestrin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D55655 mRNA. Translation: BAA23494.1.
AK313041 mRNA. Translation: BAG35873.1.
AL449264, AL450389 Genomic DNA. Translation: CAI14532.1.
AL450389, AL449264 Genomic DNA. Translation: CAI23373.1.
CH471122 Genomic DNA. Translation: EAW56635.1.
BC022288 mRNA. Translation: AAH22288.1.
RefSeqNP_001223.2. NM_001232.3.
UniGeneHs.57975.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2VAFX-ray3.80A22-399[»]
ProteinModelPortalO14958.
SMRO14958. Positions 22-370.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107295. 1 interaction.
STRING9606.ENSP00000261448.

PTM databases

PhosphoSiteO14958.

Proteomic databases

PaxDbO14958.
PRIDEO14958.

Protocols and materials databases

DNASU845.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261448; ENSP00000261448; ENSG00000118729.
GeneID845.
KEGGhsa:845.
UCSCuc001efx.4. human.

Organism-specific databases

CTD845.
GeneCardsGC01M116242.
HGNCHGNC:1513. CASQ2.
HPACAB037203.
HPA027285.
HPA055298.
MIM114251. gene.
611938. phenotype.
neXtProtNX_O14958.
Orphanet3286. Catecholaminergic polymorphic ventricular tachycardia.
PharmGKBPA26096.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG77804.
HOGENOMHOG000049047.
HOVERGENHBG050805.
InParanoidO14958.
OMAAIPNKPY.
OrthoDBEOG725DHM.
PhylomeDBO14958.
TreeFamTF313796.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressO14958.
BgeeO14958.
CleanExHS_CASQ2.
GenevestigatorO14958.

Family and domain databases

Gene3D3.40.30.10. 3 hits.
InterProIPR001393. Calsequestrin.
IPR018233. Calsequestrin_CS.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PfamPF01216. Calsequestrin. 1 hit.
[Graphical view]
PRINTSPR00312. CALSEQUESTRN.
SUPFAMSSF52833. SSF52833. 3 hits.
PROSITEPS00863. CALSEQUESTRIN_1. 1 hit.
PS00864. CALSEQUESTRIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO14958.
GenomeRNAi845.
NextBio3542.
PROO14958.
SOURCESearch...

Entry information

Entry nameCASQ2_HUMAN
AccessionPrimary (citable) accession number: O14958
Secondary accession number(s): B2R7M6, Q5T1D2, Q8TBW8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: September 19, 2002
Last modified: April 16, 2014
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM