ICAL_MOUSE
ID ICAL_MOUSE Reviewed; 788 AA.
AC P51125; Q9EQV4; Q9EQV5; Q9QXQ3; Q9QXQ4; Q9R0N1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-2002, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Calpastatin;
DE AltName: Full=Calpain inhibitor;
GN Name=Cast;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND TISSUE SPECIFICITY.
RC STRAIN=C3H/HeJ; TISSUE=Muscle;
RX PubMed=10403772; DOI=10.1006/bbrc.1999.0903;
RA Takano J., Kawamura T., Murase M., Hitomi K., Maki M.;
RT "Structure of mouse calpastatin isoforms: implications of species-common
RT and species-specific alternative splicing.";
RL Biochem. Biophys. Res. Commun. 260:339-345(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORMS 4; 5; 6 AND 7), AND TISSUE SPECIFICITY.
RX PubMed=10876161; DOI=10.1093/oxfordjournals.jbchem.a022733;
RA Takano J., Watanabe M., Hitomi K., Maki M.;
RT "Four types of calpastatin isoforms with distinct amino-terminal sequences
RT are specified by alternative first exons and differentially expressed in
RT mouse tissues.";
RL J. Biochem. 128:83-92(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORMS 4 AND 5).
RC STRAIN=CD-1;
RA Li S., Goldberg E.;
RT "Characterization of a membrane associated testis-specific calpastatin.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE OF 84-363 (ISOFORM 2).
RC STRAIN=BALB/cJ; TISSUE=Heart;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-479, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 AND THR-479, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165; SER-219; SER-303 AND
RP THR-479, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-129, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1; Synonyms=MCS-A;
CC IsoId=P51125-1; Sequence=Displayed;
CC Name=2; Synonyms=MCS-B;
CC IsoId=P51125-2; Sequence=VSP_000751;
CC Name=3; Synonyms=MCS-C;
CC IsoId=P51125-3; Sequence=VSP_000751, VSP_000752;
CC Name=4; Synonyms=TCAST1;
CC IsoId=P51125-4; Sequence=VSP_000747, VSP_000748;
CC Name=5; Synonyms=TCAST2;
CC IsoId=P51125-5; Sequence=VSP_000749, VSP_000750;
CC Name=6;
CC IsoId=P51125-6; Sequence=VSP_000745;
CC Name=7;
CC IsoId=P51125-7; Sequence=VSP_000746;
CC -!- TISSUE SPECIFICITY: Isoform 2 is the major form in all tissues
CC examined. Isoform 1 accounts for 5-10% in tissues such as skeletal
CC muscle, liver and brain, and 30% in myoblasts. Isoforms 4 and 5 are
CC testis-specific. Isoform 6 is highly expressed in heart and skeletal
CC muscle with lower levels in liver, brain and testis. Isoform 7 is
CC expressed at high levels in liver. {ECO:0000269|PubMed:10403772,
CC ECO:0000269|PubMed:10876161}.
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. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protease inhibitor I27 (calpastatin) family.
CC {ECO:0000305}.
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DR EMBL; AB026997; BAA84768.1; -; mRNA.
DR EMBL; AF190152; AAF25194.1; -; mRNA.
DR EMBL; AF190151; AAF25193.1; -; mRNA.
DR EMBL; AB044334; BAB18888.1; -; Genomic_DNA.
DR EMBL; AB044334; BAB18889.1; -; Genomic_DNA.
DR EMBL; AB044334; BAB18886.1; -; Genomic_DNA.
DR EMBL; AB044334; BAB18887.1; -; Genomic_DNA.
DR EMBL; X62519; CAA44385.1; -; mRNA.
DR CCDS; CCDS88487.1; -. [P51125-5]
DR CCDS; CCDS88491.1; -. [P51125-1]
DR PIR; S20610; S20610.
DR RefSeq; NP_001288082.1; NM_001301153.1. [P51125-1]
DR RefSeq; NP_001288089.1; NM_001301160.1. [P51125-5]
DR RefSeq; NP_001288110.1; NM_001301181.1. [P51125-4]
DR RefSeq; XP_006517122.1; XM_006517059.1. [P51125-2]
DR RefSeq; XP_011242768.1; XM_011244466.2. [P51125-6]
DR RefSeq; XP_011242769.1; XM_011244467.2. [P51125-7]
DR AlphaFoldDB; P51125; -.
DR SMR; P51125; -.
DR BioGRID; 198509; 13.
DR IntAct; P51125; 1.
DR MINT; P51125; -.
DR STRING; 10090.ENSMUSP00000065275; -.
DR MEROPS; I27.001; -.
DR MEROPS; I27.002; -.
DR MEROPS; I27.003; -.
DR MEROPS; I27.004; -.
DR iPTMnet; P51125; -.
DR PhosphoSitePlus; P51125; -.
DR CPTAC; non-CPTAC-3825; -.
DR EPD; P51125; -.
DR jPOST; P51125; -.
DR MaxQB; P51125; -.
DR PaxDb; P51125; -.
DR PeptideAtlas; P51125; -.
DR PRIDE; P51125; -.
DR ProteomicsDB; 273251; -. [P51125-1]
DR ProteomicsDB; 273252; -. [P51125-2]
DR ProteomicsDB; 273253; -. [P51125-3]
DR ProteomicsDB; 273254; -. [P51125-4]
DR ProteomicsDB; 273255; -. [P51125-5]
DR ProteomicsDB; 273256; -. [P51125-6]
DR ProteomicsDB; 273257; -. [P51125-7]
DR Antibodypedia; 4008; 423 antibodies from 33 providers.
DR DNASU; 12380; -.
DR Ensembl; ENSMUST00000223206; ENSMUSP00000152174; ENSMUSG00000021585. [P51125-1]
DR Ensembl; ENSMUST00000223309; ENSMUSP00000152657; ENSMUSG00000021585. [P51125-5]
DR GeneID; 12380; -.
DR KEGG; mmu:12380; -.
DR UCSC; uc007rfl.2; mouse. [P51125-4]
DR UCSC; uc007rfq.2; mouse. [P51125-1]
DR CTD; 831; -.
DR MGI; MGI:1098236; Cast.
DR VEuPathDB; HostDB:ENSMUSG00000021585; -.
DR eggNOG; ENOG502RHIZ; Eukaryota.
DR GeneTree; ENSGT00390000002993; -.
DR InParanoid; P51125; -.
DR OMA; IKEKDHT; -.
DR PhylomeDB; P51125; -.
DR Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
DR BioGRID-ORCS; 12380; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Cast; mouse.
DR PRO; PR:P51125; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P51125; protein.
DR Bgee; ENSMUSG00000021585; Expressed in spermatid and 229 other tissues.
DR ExpressionAtlas; P51125; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0010859; F:calcium-dependent cysteine-type endopeptidase inhibitor activity; ISO:MGI.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0007343; P:egg activation; ISO:MGI.
DR GO; GO:0097340; P:inhibition of cysteine-type endopeptidase activity; ISO:MGI.
DR GO; GO:0043086; P:negative regulation of catalytic activity; ISO:MGI.
DR GO; GO:0010466; P:negative regulation of peptidase activity; IGI:MGI.
DR GO; GO:2000675; P:negative regulation of type B pancreatic cell apoptotic process; ISO:MGI.
DR GO; GO:0030163; P:protein catabolic process; ISA:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:MGI.
DR InterPro; IPR026998; Calpastatin.
DR InterPro; IPR001259; Prot_inh_calpain.
DR PANTHER; PTHR10077; PTHR10077; 1.
DR Pfam; PF00748; Calpain_inhib; 3.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Isopeptide bond; Phosphoprotein;
KW Protease inhibitor; Reference proteome; Repeat; Thiol protease inhibitor;
KW Ubl conjugation.
FT CHAIN 1..788
FT /note="Calpastatin"
FT /id="PRO_0000147633"
FT REPEAT 251..303
FT /note="Inhibitory domain 1"
FT REPEAT 384..436
FT /note="Inhibitory domain 2"
FT REPEAT 524..577
FT /note="Inhibitory domain 3"
FT REPEAT 661..714
FT /note="Inhibitory domain 4"
FT REGION 1..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 514..580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 620..788
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..93
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 100..143
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..179
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 216..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 233..255
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 314..330
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 352..366
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 370..389
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 394..444
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 471..485
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 522..574
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 637..730
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 733..753
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 755..788
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19131326"
FT MOD_RES 129
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 216
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P27321"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 324
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 444
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 479
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079"
FT MOD_RES 518
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 594
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 605
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 653
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT MOD_RES 655
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT CROSSLNK 112
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P20810"
FT VAR_SEQ 1..357
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_000749"
FT VAR_SEQ 1..341
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_000747"
FT VAR_SEQ 1..83
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000305"
FT /id="VSP_000746"
FT VAR_SEQ 1..25
FT /note="MSQPGPKPAASPRPSRGAAARHTQE -> MAFASWWYKT (in isoform
FT 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_000745"
FT VAR_SEQ 92..110
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10403772"
FT /id="VSP_000751"
FT VAR_SEQ 305..333
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10403772"
FT /id="VSP_000752"
FT VAR_SEQ 342..396
FT /note="AQSAGVTRSSVPPKEKKRKVEEEVINDQALQALSDSLGTRQPDPPSHVSQAE
FT QVK -> MGQFLSSTFWEGSPAAVWQEKLREGERKGAGETIPILQDHVICSEEREHGSK
FT HH (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_000748"
FT VAR_SEQ 358..397
FT /note="KRKVEEEVINDQALQALSDSLGTRQPDPPSHVSQAEQVKE -> MGQFLSST
FT FWEGSPAAVWQEKLREGERKGAGETIPILQDH (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_000750"
SQ SEQUENCE 788 AA; 84922 MW; 28E4D3B4A68BFEB9 CRC64;
MSQPGPKPAA SPRPSRGAAA RHTQEHVNEK NIGSSSKPGE KKGSDEKKAA SLGSSQPSRP
HVGEAATATK VTASSAATSK SPSMSTTETK AIPVNKQLEG PDQKRPREQA VKTESKKPQS
SEQPVVHEKK SKGGPKEGSE PKNLPKHTSS TGSKHAHKEK ALSRSNEQMV SEKPSESKTK
FQDVPSAGGE SVAGGGTVAT ALDKVVGKKK EQKPFTPASP VQSTPSKPSD KSGMDAALDD
LIDTLGGHED TNRDDPPYTG PVVLDPMYST YLEALGIKEG TIPPEYRKLL EKNEGITQPL
PDSPKPMGTD QAIDALSSDF TCSSPTGKQS EKEKSTGEIF KAQSAGVTRS SVPPKEKKRK
VEEEVINDQA LQALSDSLGT RQPDPPSHVS QAEQVKEAKA KEERQEKCGE DEDTVPAEYR
LKPAKDKDGK PLLPEPEETS KSLSESELIG ELSADFDRST YQDKPSTPAE KKSNDTSQTP
PGETVPRASM CSIRSAPPKL ASLKGVVPED AVETLAGSLG TREADPEHEK TVEDKVKEKA
KEEEHEKLGE KEETVPPDYR LEEVKDKDGK PLLPKESQEQ LAPLSDDFLL DALSQDFSSP
ANISSLEFED AKLSAAISEV VSQTPAPSTH AAAPLPGTEQ KDKELDDALD ELSDSLGQRP
PDPDENKPLD DKVKEKIKPE HSEKLGERDD TIPPEYRHLL DNDGKDKPEK PPTKKTEKPD
QDRDPIDALS EDLDSCPSTT ETSKNTAKGK SKKTSSSKAS KDGEKTKDSS KKTEEVSKPK
AKEDARHS
