[1]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Heart; Tanaka T., Inazawa J., Nakamura Y.; "Molecular cloning of a human cDNA for cardiac calsequestrin and its chromosomal assignment to 1p13.3 by fluorescence in situ hybridization."; Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases.
[2]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Skeletal muscle; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[3]	X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) OF 22-399, SUBUNIT, FUNCTION, CHARACTERIZATION OF VARIANTS CPVT2 GLN-33; HIS-167 AND HIS-307, AND CHARACTERIZATION OF VARIANTS ALA-66 AND MET-76. DOI=10.1016/j.jmb.2007.08.055; PubMed=17881003 [NCBI, ExPASy, EBI, Israel, Japan] Kim E., Youn B., Kemper L., Campbell C., Milting H., Varsanyi M., Kang C.; "Characterization of human cardiac calsequestrin and its deleterious mutants."; J. Mol. Biol. 373:1047-1057(2007).
[4]	VARIANT CPVT2 HIS-307. DOI=10.1086/324565; PubMed=11704930 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "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."; Am. J. Hum. Genet. 69:1378-1384(2001).
[5]	VARIANTS ALA-66 AND MET-76. DOI=10.1038/sj.ejhg.5201061; PubMed=14571276 [NCBI, ExPASy, EBI, Israel, Japan] Laitinen P.J., Swan H., Kontula K.; "Molecular genetics of exercise-induced polymorphic ventricular tachycardia: identification of three novel cardiac ryanodine receptor mutations and two common calsequestrin 2 amino-acid polymorphisms."; Eur. J. Hum. Genet. 11:888-891(2003).
[6]	CHARACTERIZATION OF VARIANT CPVT2 HIS-307. DOI=10.1016/j.cardiores.2004.09.009; PubMed=15485681 [NCBI, ExPASy, EBI, Israel, Japan] Houle T.D., Ram M.L., Cala S.E.; "Calsequestrin mutant D307H exhibits depressed binding to its protein targets and a depressed response to calcium."; Cardiovasc. Res. 64:227-233(2004).
[7]	VARIANT CPVT2 HIS-167, AND CHARACTERIZATION OF VARIANT CPVT2 HIS-167. DOI=10.1161/CIRCULATIONAHA.106.623793; PubMed=16908766 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Clinical phenotype and functional characterization of CASQ2 mutations associated with catecholaminergic polymorphic ventricular tachycardia."; Circulation 114:1012-1019(2006).
[8]	VARIANTS CPVT2 GLN-33 AND HIS-167, AND CHARACTERIZATION OF ARIANTS CPVT2 GLN-33 AND HIS-167. DOI=10.1042/BJ20080163; PubMed=18399795 [NCBI, ExPASy, EBI, Israel, Japan] Valle G., Galla D., Nori A., Priori S.G., Gyorke S., de Filippis V., Volpe P.; "Catecholaminergic polymorphic ventricular tachycardia-related mutations R33Q and L167H alter calcium sensitivity of human cardiac calsequestrin."; Biochem. J. 413:291-303(2008).

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. Binds 40 to 50 moles of calcium.
SUBUNIT: 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.
SUBCELLULAR LOCATION: Sarcoplasmic reticulum lumen. Note=This isoform of calsequestrin occurs in the sarcoplasmic reticulum's terminal cisternae luminal spaces of cardiac and slow skeletal muscle cells.
DISEASE: Defects in CASQ2 are the cause of catecholaminergic polymorphic ventricular tachycardia type 2 (CPVT2) [MIM:611938]; also known as stress-induced polymorphic ventricular tachycardia (VTSIP). CPVT2 is an autosomal recessive form of arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death.
SIMILARITY: Belongs to the calsequestrin family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=CASQ2";.
WEB RESOURCE: Name=Wikipedia; Note=Calsequestrin entry; URL="http://en.wikipedia.org/wiki/Calsequestrin";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

D55655; BAA23494.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC022288; AAH22288.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI00298933; -.

NP_001223.2; -.

3D structure databases

PDB

2VAF; X-ray; 3.80 A; A=22-399.

[ExPASy / RCSB / EBI]

2VAF; -.

PTM databases

O14958; -.

Organism-specific databases

GC01M116044; -.

HIX0000921; -.

HGNC:1513; CASQ2.

114251; gene. [NCBI / EBI]
611938; phenotype. [NCBI / EBI]

Orphanet

3286; Polymorphic catecholergic ventricular tachycardia.

PharmGKB

PA26096; -.

Gene expression databases

O14958; -.

O14958; -.

HS_CASQ2; -.

ENSG00000118729; Homo sapiens.

Ontologies

GO:0033018;	Cellular component: sarcoplasmic reticulum lumen (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005509;	Molecular function: calcium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0007507;	Biological process: heart development (traceable author statement from ProtInc).
GO:0006941;	Biological process: striated muscle contraction (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR001393; Calsequestrin.
IPR018233; Calsequestrin_CS.
IPR012335; Thioredoxin_fold.
Graphical view of domain structure.

Gene3D

G3DSA:3.40.30.10; Thioredoxin_fold; 3.

PANTHER

PTHR10033; Calsequestrin; 1.

Pfam

PF01216; Calsequestrin; 1.
Pfam graphical view of domain structure.

PRINTS

PR00312; CALSEQUESTRN.

PROSITE

PS00863; CALSEQUESTRIN_1; 1.
PS00864; CALSEQUESTRIN_2; 1.

Proteomic databases

PRIDE

O14958; -.

Genome annotation databases

Ensembl

ENSG00000118729; Homo sapiens. [Contig view]

GeneID

845; -.

KEGG

hsa:845; -.

Phylogenomic databases

HOGENOM

O14958; -.

HOVERGEN

O14958; -.

OMA

O14958; EGIHIVA.

Other

3542; -.

CASQ2; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Calcium; Disease mutation; Glycoprotein; Muscle protein; Polymorphism; Sarcoplasmic reticulum; Signal.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 19`	`19`	`By similarity.`
`CHAIN`	`20 399`	`380`	`Calsequestrin-2.`	`PRO_0000004218`
`COMPBIAS`	`356 399`	`44`	`Asp/Glu-rich (acidic).`
`CARBOHYD`	`335 335`		`N-linked (GlcNAc...) (Potential).`
`VARIANT`	`33 33`	`1`	`R -> Q (in CPVT2; reduces calcium-dependent dimerization).`	`VAR_055234`
`VARIANT`	`66 66`	`1`	`T -> A (in dbSNP:rs4074536 [NCBI]).`	`VAR_023692`
`VARIANT`	`76 76`	`1`	`V -> M (in dbSNP:rs10801999 [NCBI]).`	`VAR_023693`
`VARIANT`	`167 167`	`1`	`L -> 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).`	`VAR_044118`
`VARIANT`	`307 307`	`1`	`D -> H (in CPVT2; reduces calcium-binding and causes 50% decrease in calcium-dependent binding to triadin-1 and junctin).`	`VAR_016075`
`CONFLICT`	`67 67`		`Q -> P (in Ref. 1; BAA23494).`
`STRAND`	`23 38`	`16`
`HELIX`	`39 48`	`10`
`STRAND`	`49 66`	`18`
`HELIX`	`67 84`	`18`
`STRAND`	`85 97`	`13`
`HELIX`	`98 103`	`6`
`STRAND`	`104 130`	`27`
`HELIX`	`131 141`	`11`
`STRAND`	`142 152`	`11`
`HELIX`	`153 158`	`6`
`STRAND`	`159 176`	`18`
`HELIX`	`177 188`	`12`
`STRAND`	`189 200`	`12`
`HELIX`	`201 207`	`7`
`STRAND`	`208 217`	`10`
`STRAND`	`219 223`	`5`
`STRAND`	`229 233`	`5`
`HELIX`	`234 243`	`10`
`STRAND`	`248 252`	`5`
`HELIX`	`256 261`	`6`
`STRAND`	`262 278`	`17`
`HELIX`	`279 294`	`16`
`STRAND`	`295 298`	`4`
`STRAND`	`300 307`	`8`
`HELIX`	`312 320`	`9`
`STRAND`	`321 328`	`8`
`STRAND`	`330 351`	`22`
`HELIX`	`356 361`	`6`
`STRAND`	`362 369`	`8`

Sequence information

Length: 399 AA [This is the length of the unprocessed precursor]

Molecular weight: 46436 Da [This is the MW of the unprocessed precursor]

CRC64: 7794DC2FF7E4B064 [This is a checksum on the sequence]

        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

O14958 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools