ICAL_RAT
ID ICAL_RAT Reviewed; 713 AA.
AC P27321; A5GXY4; A5GXY5; A5GXY6; A5GXY7; A5GXY8; A5GXY9; A5GXZ7; O55151;
AC O55152; O55153; Q5BK19; Q99MG1; Q99MG2;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 3.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Calpastatin;
DE AltName: Full=Calpain inhibitor;
GN Name=Cast;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6 AND 7).
RC STRAIN=Sprague-Dawley;
RX PubMed=17570336; DOI=10.1016/j.abb.2007.05.007;
RA De Tullio R., Averna M., Stifanese R., Parr T., Bardsley R.G.,
RA Pontremoli S., Melloni E.;
RT "Multiple rat brain calpastatin forms are produced by distinct starting
RT points and alternative splicing of the N-terminal exons.";
RL Arch. Biochem. Biophys. 465:148-156(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 55-713 (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=2015306; DOI=10.1016/0167-4781(91)90139-d;
RA Ishida S., Emori Y., Suzuki K.;
RT "Rat calpastatin has diverged primary sequence from other mammalian
RT calpastatins but retains functionally important sequences.";
RL Biochim. Biophys. Acta 1088:436-438(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 55-713 (ISOFORMS 1; 2 AND 5).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=9475181; DOI=10.1016/s0014-5793(97)01588-3;
RA De Tullio R., Sparatore B., Salamino F., Melloni E., Pontremoli S.;
RT "Rat brain contains multiple mRNAs for calpastatin.";
RL FEBS Lett. 422:113-117(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 59-713 (ISOFORMS 1 AND 5).
RC STRAIN=Sprague-Dawley; TISSUE=Heart;
RA Risbood M.P., Lin H., Lee T.;
RT "Hypoxic induction of two rat cardiac calpastatin cDNAs.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 60-188 (ISOFORMS 1; 2 AND 4).
RC STRAIN=Fischer;
RX PubMed=1730065; DOI=10.1016/0167-4781(92)90500-y;
RA Lee W.J., Hatanaka M., Maki M.;
RT "Multiple forms of rat calpastatin cDNA in the coding region of
RT functionally unknown amino-terminal domain.";
RL Biochim. Biophys. Acta 1129:251-253(1992).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-57; SER-122; SER-171;
RP THR-173; SER-260; SER-580 AND SER-582, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 193-278 IN COMPLEX WITH CAPN2 AND
RP CAPNS1.
RX PubMed=19020622; DOI=10.1038/nature07353;
RA Moldoveanu T., Gehring K., Green D.R.;
RT "Concerted multi-pronged attack by calpastatin to occlude the catalytic
RT cleft of heterodimeric calpains.";
RL Nature 456:404-408(2008).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 571-664 IN COMPLEX WITH CAPN2 AND
RP CAPNS1, INHIBITORY DOMAINS, AND MUTAGENESIS OF GLY-613.
RX PubMed=19020623; DOI=10.1038/nature07451;
RA Hanna R.A., Campbell R.L., Davies P.L.;
RT "Calcium-bound structure of calpain and its mechanism of inhibition by
RT calpastatin.";
RL Nature 456:409-412(2008).
CC -!- FUNCTION: Specific inhibition of calpain (calcium-dependent cysteine
CC protease). Plays a key role in postmortem tenderization of meat and
CC have been proposed to be involved in muscle protein degradation in
CC living tissue.
CC -!- INTERACTION:
CC P27321; Q07009: Capn2; NbExp=10; IntAct=EBI-7441624, EBI-1040438;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1; Synonyms=A;
CC IsoId=P27321-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=P27321-2; Sequence=VSP_000754;
CC Name=3; Synonyms=C;
CC IsoId=P27321-3; Sequence=VSP_026972;
CC Name=4;
CC IsoId=P27321-4; Sequence=VSP_000753, VSP_000754;
CC Name=5;
CC IsoId=P27321-5; Sequence=VSP_000754, VSP_026972;
CC Name=6;
CC IsoId=P27321-6; Sequence=VSP_000753, VSP_000754, VSP_026972;
CC Name=7;
CC IsoId=P27321-7; Sequence=VSP_026971;
CC -!- DOMAIN: Each of the four flexible inhibitory domains can inhibit one
CC calcium-bound calpain molecule by occupying both sides of the active
CC site.
CC -!- SIMILARITY: Belongs to the protease inhibitor I27 (calpastatin) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK29411.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAK29412.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA40053.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA40053.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA73915.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA73916.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA73917.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; DQ186624; ABA86879.1; -; mRNA.
DR EMBL; DQ186625; ABA86880.1; -; mRNA.
DR EMBL; DQ186626; ABA86881.1; -; mRNA.
DR EMBL; DQ186627; ABA86882.1; -; mRNA.
DR EMBL; DQ186628; ABA86883.1; -; mRNA.
DR EMBL; DQ186629; ABA86884.1; -; mRNA.
DR EMBL; DQ287975; ABB90254.1; -; mRNA.
DR EMBL; BC091239; AAH91239.1; -; mRNA.
DR EMBL; X56729; CAA40053.1; ALT_SEQ; mRNA.
DR EMBL; Y13587; CAA73915.1; ALT_INIT; mRNA.
DR EMBL; Y13588; CAA73916.1; ALT_INIT; mRNA.
DR EMBL; Y13589; CAA73917.1; ALT_INIT; mRNA.
DR EMBL; AF346597; AAK29411.1; ALT_INIT; mRNA.
DR EMBL; AF346598; AAK29412.1; ALT_INIT; mRNA.
DR EMBL; X62520; CAA44386.1; -; mRNA.
DR PIR; S15074; S15074.
DR PIR; S20611; S20611.
DR RefSeq; NP_001028887.1; NM_001033715.1.
DR RefSeq; NP_001028888.1; NM_001033716.1.
DR RefSeq; NP_445747.2; NM_053295.2.
DR PDB; 3BOW; X-ray; 2.40 A; C=571-664.
DR PDB; 3DF0; X-ray; 2.95 A; C=193-278.
DR PDBsum; 3BOW; -.
DR PDBsum; 3DF0; -.
DR AlphaFoldDB; P27321; -.
DR SMR; P27321; -.
DR DIP; DIP-44338N; -.
DR IntAct; P27321; 1.
DR MINT; P27321; -.
DR STRING; 10116.ENSRNOP00000058759; -.
DR MEROPS; I27.001; -.
DR MEROPS; I27.002; -.
DR MEROPS; I27.003; -.
DR iPTMnet; P27321; -.
DR PhosphoSitePlus; P27321; -.
DR jPOST; P27321; -.
DR PaxDb; P27321; -.
DR PeptideAtlas; P27321; -.
DR PRIDE; P27321; -.
DR GeneID; 25403; -.
DR KEGG; rno:25403; -.
DR CTD; 831; -.
DR RGD; 2278; Cast.
DR eggNOG; ENOG502RHIZ; Eukaryota.
DR InParanoid; P27321; -.
DR OrthoDB; 203890at2759; -.
DR PhylomeDB; P27321; -.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR EvolutionaryTrace; P27321; -.
DR PRO; PR:P27321; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0016020; C:membrane; IDA:ARUK-UCL.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:ARUK-UCL.
DR GO; GO:0010859; F:calcium-dependent cysteine-type endopeptidase inhibitor activity; IDA:RGD.
DR GO; GO:0002020; F:protease binding; IDA:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0007343; P:egg activation; IDA:RGD.
DR GO; GO:0097340; P:inhibition of cysteine-type endopeptidase activity; ISO:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0045445; P:myoblast differentiation; IEP:RGD.
DR GO; GO:0007520; P:myoblast fusion; IEP:RGD.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:RGD.
DR GO; GO:0010466; P:negative regulation of peptidase activity; ISO:RGD.
DR GO; GO:2000675; P:negative regulation of type B pancreatic cell apoptotic process; ISO:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:RGD.
DR GO; GO:0042176; P:regulation of protein catabolic process; TAS:RGD.
DR DisProt; DP01994; -.
DR InterPro; IPR026998; Calpastatin.
DR InterPro; IPR001259; Prot_inh_calpain.
DR PANTHER; PTHR10077; PTHR10077; 2.
DR Pfam; PF00748; Calpain_inhib; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Isopeptide bond;
KW Phosphoprotein; Protease inhibitor; Reference proteome; Repeat;
KW Thiol protease inhibitor; Ubl conjugation.
FT CHAIN 1..713
FT /note="Calpastatin"
FT /id="PRO_0000147635"
FT REPEAT 208..260
FT /note="Inhibitory domain 1"
FT REPEAT 341..393
FT /note="Inhibitory domain 2"
FT REPEAT 451..504
FT /note="Inhibitory domain 3"
FT REPEAT 588..641
FT /note="Inhibitory domain 4"
FT REGION 1..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 253..402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 442..507
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 544..713
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 47..77
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..100
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 107..136
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 327..346
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 347..401
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 442..502
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 563..652
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 673..713
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 86
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51125"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 171
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 173
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 260
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 410
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 445
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 532
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 580
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 582
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CROSSLNK 69
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT VAR_SEQ 1..177
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:17570336"
FT /id="VSP_026971"
FT VAR_SEQ 67..79
FT /note="Missing (in isoform 4 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:1730065,
FT ECO:0000303|PubMed:17570336"
FT /id="VSP_000753"
FT VAR_SEQ 98..135
FT /note="Missing (in isoform 2, isoform 4, isoform 5 and
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1730065, ECO:0000303|PubMed:17570336,
FT ECO:0000303|PubMed:9475181, ECO:0000303|Ref.5"
FT /id="VSP_000754"
FT VAR_SEQ 166..188
FT /note="Missing (in isoform 3, isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:17570336,
FT ECO:0000303|PubMed:9475181, ECO:0000303|Ref.5"
FT /id="VSP_026972"
FT MUTAGEN 613
FT /note="G->A: 2.9-fold increase in the IC(50)."
FT /evidence="ECO:0000269|PubMed:19020623"
FT MUTAGEN 613
FT /note="G->FG: Turns CAST from an inhibitor into a
FT substrate."
FT /evidence="ECO:0000269|PubMed:19020623"
FT CONFLICT 161
FT /note="K -> E (in Ref. 1; CAA40053 and 5; AAK29411)"
FT /evidence="ECO:0000305"
FT CONFLICT 209
FT /note="N -> S (in Ref. 4; CAA73917)"
FT /evidence="ECO:0000305"
FT CONFLICT 314
FT /note="K -> E (in Ref. 5; AAK29412)"
FT /evidence="ECO:0000305"
FT CONFLICT 463
FT /note="V -> G (in Ref. 1; ABA86879/ABA86880/ABA86881/
FT ABA86882/ABA86883/ABA86884/ABB90254 and 4; CAA73916)"
FT /evidence="ECO:0000305"
FT CONFLICT 481
FT /note="T -> A (in Ref. 4; CAA73917)"
FT /evidence="ECO:0000305"
FT CONFLICT 518
FT /note="D -> G (in Ref. 4; CAA73917)"
FT /evidence="ECO:0000305"
FT CONFLICT 611
FT /note="K -> R (in Ref. 4; CAA73915)"
FT /evidence="ECO:0000305"
FT CONFLICT 646
FT /note="L -> P (in Ref. 2; AAH91239, 4; CAA73915/CAA73917
FT and 5; AAK29411/AAK29412)"
FT /evidence="ECO:0000305"
FT HELIX 195..199
FT /evidence="ECO:0007829|PDB:3DF0"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:3DF0"
FT HELIX 241..247
FT /evidence="ECO:0007829|PDB:3DF0"
FT HELIX 271..274
FT /evidence="ECO:0007829|PDB:3DF0"
FT TURN 275..277
FT /evidence="ECO:0007829|PDB:3DF0"
FT HELIX 573..581
FT /evidence="ECO:0007829|PDB:3BOW"
FT HELIX 616..618
FT /evidence="ECO:0007829|PDB:3BOW"
FT HELIX 621..627
FT /evidence="ECO:0007829|PDB:3BOW"
FT HELIX 652..659
FT /evidence="ECO:0007829|PDB:3BOW"
SQ SEQUENCE 713 AA; 77313 MW; 55505300F59A8DE3 CRC64;
MSRPGPKPAA SSRPRRGAAA SHTQEHVNEK NIGSSSKPAE KKGSDEVTAS SAATGTSPRM
STTGAKAVKI ESEKSQSSEP PVIHEKKPKG KPKEGSEPQT LPKHASDTGS KHAHKEKALS
RSNEQIVSEK SSESKTKFQD APSADGESVA GGVTVATASD KVVVKKKEKK SLTPTLPMES
TLNKLSDKSG VNAALDDLID TLGECEDTNK DDPPYTGPVV LDPMDSTYLE ALGIKEGTIP
PEYRKLLEKN EAITGPLPDS PKPMGIDHAI DALSSDFTCS SPTGKQTEKE KSTGESSKAQ
SAGVTRSAVP PQEKKRKVEE EVMNDQALQA LSDSLGTRQP DPQSHLRQAK QVKEAKAKEE
RQEKCGEDED TVPAEYRLKP AKDKDGKPLL PEPEETSKCL SESELIGELS ADFVQPTYQE
KPSMPAAKIK KGVVPDDAVE TLARSLGTRK EDPEDEKSLV DKVKEKAKEE DHEKLGEKEE
TIPPDYRLEI VKDKDGKPLL PKEAEEQLPP LSDDFLLDAL SQDFSSPANI LSLGFEDAKL
SAAVSETVSQ VPAPSNHTAA PPPGTERRDK ELDDALDELS DSLGQRQPDP DENKPLDDKV
KEKIKAEHSE KLGERDDTIP PEYRHLLDND GKDKPEKPLT KNTEKLGQDQ DPIDALSEDL
DSCPPTTETS QNTTKEKGKK TSSSKASKNE EKTKDSSKKT EEVPKPKVDE DAT
