CASQ2_CANLF
ID CASQ2_CANLF Reviewed; 410 AA.
AC P12637;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Calsequestrin-2;
DE AltName: Full=Calsequestrin, cardiac muscle isoform;
DE Flags: Precursor;
GN Name=CASQ2;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=3379055; DOI=10.1016/s0021-9258(18)68401-7;
RA Scott B.T., Simmerman H.K.B., Collins J.H., Nadal-Ginard B., Jones L.R.;
RT "Complete amino acid sequence of canine cardiac calsequestrin deduced by
RT cDNA cloning.";
RL J. Biol. Chem. 263:8958-8964(1988).
RN [2]
RP PROTEIN SEQUENCE OF 20-71, FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=3427023; DOI=10.1021/bi00394a038;
RA Slupsky J.R., Ohnishi M., Carpenter M.R., Reithmeier R.A.F.;
RT "Characterization of cardiac calsequestrin.";
RL Biochemistry 26:6539-6544(1987).
RN [3]
RP PHOSPHORYLATION AT SER-397; SER-401 AND SER-405 BY CK2.
RX PubMed=1985907; DOI=10.1016/s0021-9258(18)52447-9;
RA Cala S.E., Jones L.R.;
RT "Phosphorylation of cardiac and skeletal muscle calsequestrin isoforms by
RT casein kinase II. Demonstration of a cluster of unique rapidly
RT phosphorylated sites in cardiac calsequestrin.";
RL J. Biol. Chem. 266:391-398(1991).
RN [4]
RP FUNCTION, MUTAGENESIS OF LYS-206, GLYCOSYLATION, AND INTERACTION WITH TRDN.
RX PubMed=20302875; DOI=10.1016/j.yjmcc.2010.03.006;
RA Kirchhefer U., Wehrmeister D., Postma A.V., Pohlentz G., Mormann M.,
RA Kucerova D., Muller F.U., Schmitz W., Schulze-Bahr E., Wilde A.A.,
RA Neumann J.;
RT "The human CASQ2 mutation K206N is associated with hyperglycosylation and
RT altered cellular calcium handling.";
RL J. Mol. Cell. Cardiol. 49:95-105(2010).
RN [5]
RP GLYCOSYLATION.
RX PubMed=21431367; DOI=10.1007/s11010-011-0777-6;
RA McFarland T.P., Sleiman N.H., Yaeger D.B., Cala S.E.;
RT "The cytosolic protein kinase CK2 phosphorylates cardiac calsequestrin in
RT intact cells.";
RL Mol. Cell. Biochem. 353:81-91(2011).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 22-371, FUNCTION, SUBUNIT, AND
RP CALCIUM AFFINITY.
RX PubMed=14871888; DOI=10.1074/jbc.m311553200;
RA Park H., Park I.Y., Kim E., Youn B., Fields K., Dunker A.K., Kang C.;
RT "Comparing skeletal and cardiac calsequestrin structures and their calcium
RT binding: a proposed mechanism for coupled calcium binding and protein
RT polymerization.";
RL J. Biol. Chem. 279:18026-18033(2004).
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:3427023). Calcium ions are bound by clusters of acidic residues
CC at the protein surface, especially at the interface between subunits.
CC Can bind around 60 Ca(2+) ions. Regulates the release of lumenal Ca(2+)
CC via the calcium release channel RYR2; this plays an important role in
CC triggering muscle contraction. Plays a role in excitation-contraction
CC coupling in the heart and in regulating the rate of heart beats.
CC {ECO:0000269|PubMed:14871888, ECO:0000269|PubMed:20302875,
CC ECO:0000269|PubMed:3427023}.
CC -!- SUBUNIT: Interacts with ASPH (By similarity). Monomer, homodimer and
CC homooligomer. Mostly monomeric in the absence of calcium. Forms higher
CC oligomers in a calcium-dependent manner. Dimers associate to form
CC tetramers, that then form linear homomer chains. Interacts with TRDN.
CC {ECO:0000250|UniProtKB:O14958, ECO:0000269|PubMed:14871888,
CC ECO:0000269|PubMed:20302875}.
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:O09161}. Note=This isoform of calsequestrin
CC occurs in the sarcoplasmic reticulum's terminal cisternae luminal
CC spaces of cardiac and slow skeletal muscle cells.
CC {ECO:0000250|UniProtKB:O09161}.
CC -!- TISSUE SPECIFICITY: Detected in heart muscle (at protein level).
CC {ECO:0000269|PubMed:3427023}.
CC -!- PTM: Phosphorylation in the C-terminus, probably by CK2, moderately
CC increases calcium buffering capacity. {ECO:0000250|UniProtKB:O14958}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:20302875,
CC ECO:0000269|PubMed:21431367}.
CC -!- SIMILARITY: Belongs to the calsequestrin family. {ECO:0000305}.
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DR EMBL; J03766; AAA30833.1; -; mRNA.
DR PIR; A28071; A28071.
DR PIR; A39040; A39040.
DR RefSeq; NP_001300745.1; NM_001313816.1.
DR PDB; 1SJI; X-ray; 2.40 A; A/B=22-371.
DR PDBsum; 1SJI; -.
DR AlphaFoldDB; P12637; -.
DR SMR; P12637; -.
DR CORUM; P12637; -.
DR STRING; 9615.ENSCAFP00000051055; -.
DR iPTMnet; P12637; -.
DR PaxDb; P12637; -.
DR GeneID; 483134; -.
DR KEGG; cfa:483134; -.
DR CTD; 845; -.
DR eggNOG; ENOG502QU4Q; Eukaryota.
DR InParanoid; P12637; -.
DR OrthoDB; 1091027at2759; -.
DR EvolutionaryTrace; P12637; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0033018; C:sarcoplasmic reticulum lumen; IBA:GO_Central.
DR GO; GO:0030018; C:Z disc; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0060315; P:negative regulation of ryanodine-sensitive calcium-release channel activity; IDA:BHF-UCL.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; IBA:GO_Central.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IBA:GO_Central.
DR GO; GO:0010880; P:regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IDA:BHF-UCL.
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; Glycoprotein;
KW Metal-binding; Muscle protein; Phosphoprotein; Reference proteome;
KW Sarcoplasmic reticulum; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:3427023"
FT CHAIN 20..410
FT /note="Calsequestrin-2"
FT /id="PRO_0000004217"
FT REGION 221..242
FT /note="Calcium regulated hydrophobic site"
FT REGION 364..410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 374..410
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 282
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O09161"
FT MOD_RES 397
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:1985907"
FT MOD_RES 401
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:1985907"
FT MOD_RES 405
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:1985907"
FT CARBOHYD 335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 395
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 206
FT /note="K->N: Creates an additional N-glycosylation site.
FT Decreases calcium binding and increases the rate of
FT spontaneous Ca(2+) release from myocytes."
FT /evidence="ECO:0000269|PubMed:20302875"
FT CONFLICT 71
FT /note="Q -> E (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 39..46
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 50..57
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 68..83
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 87..95
FT /evidence="ECO:0007829|PDB:1SJI"
FT TURN 96..99
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 100..106
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 113..118
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 131..139
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 152..160
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 177..188
FT /evidence="ECO:0007829|PDB:1SJI"
FT TURN 189..192
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 193..198
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 201..207
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 214..217
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 234..244
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 248..251
FT /evidence="ECO:0007829|PDB:1SJI"
FT TURN 254..256
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 257..262
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 265..273
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 279..294
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 303..306
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 308..310
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 312..321
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 330..339
FT /evidence="ECO:0007829|PDB:1SJI"
FT STRAND 341..344
FT /evidence="ECO:0007829|PDB:1SJI"
FT HELIX 355..366
FT /evidence="ECO:0007829|PDB:1SJI"
SQ SEQUENCE 410 AA; 47417 MW; FCA99A8D7E7ABB82 CRC64;
MKRTHLFIAG LYLLASCRAE EGLNFPTYDG KDRVVSLTEK NFKQVLKKYD VLCLYYHESV
SSDKVAQKQF QLKEIVLELV AQVLEHKDIG FVMVDAKKEA KLAKKLGFDE EGSLYVLKGD
RTIEFDGEFA ADVLVEFLLD LIEDPVEIIN SKLEVQAFER IEDQIKLIGF FKSEESEYYK
AFEEAAEHFQ PYIKFFATFD KGVAKKLSLK MNEVDFYEPF MDEPIAIPDK PYTEEELVEF
VKEHQRPTLR RLRPEDMFET WEDDLNGIHI VAFAERSDPD GYEFLEILKQ VARDNTDNPD
LSIVWIDPDD FPLLVAYWEK TFKIDLFKPQ IGVVNVTDAD SVWMEIPDDD DLPTAEELED
WIEDVLSGKI NTEDDDNEEG DDGDDDEDDD DDDGNNSDEE SNDDSDDDDE
