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 27-MAR-2024, entry version 163. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyCosmos; P12637; 2 sites, No reported glycans. DR iPTMnet; P12637; -. DR PaxDb; 9612-ENSCAFP00000014348; -. DR GeneID; 483134; -. DR KEGG; cfa:483134; -. DR CTD; 845; -. DR eggNOG; ENOG502QU4Q; Eukaryota. DR InParanoid; P12637; -. DR OrthoDB; 2873811at2759; -. DR EvolutionaryTrace; P12637; -. DR Proteomes; UP000002254; Unplaced. DR Proteomes; UP000694429; Unplaced. DR Proteomes; UP000694542; Unplaced. DR Proteomes; UP000805418; 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: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 Gene3D; 3.40.30.10; Glutaredoxin; 3. 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 PANTHER; PTHR10033; CALSEQUESTRIN; 1. DR PANTHER; PTHR10033:SF15; CALSEQUESTRIN-2; 1. DR Pfam; PF01216; Calsequestrin; 1. DR PRINTS; PR00312; CALSEQUESTRN. DR SUPFAM; SSF52833; Thioredoxin-like; 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 //