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P27321

- ICAL_RAT

UniProt

P27321 - ICAL_RAT

Protein

Calpastatin

Gene

Cast

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 107 (01 Oct 2014)
      Sequence version 3 (24 Jul 2007)
      Previous versions | rss
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    Functioni

    Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue.

    GO - Molecular functioni

    1. calcium-dependent cysteine-type endopeptidase inhibitor activity Source: RGD
    2. protease binding Source: RGD
    3. protein binding Source: IntAct

    GO - Biological processi

    1. aging Source: RGD
    2. brain development Source: RGD
    3. egg activation Source: RGD
    4. liver development Source: RGD
    5. myoblast differentiation Source: RGD
    6. myoblast fusion Source: RGD
    7. negative regulation of catalytic activity Source: RGD
    8. negative regulation of cell cycle arrest Source: RGD
    9. negative regulation of endopeptidase activity Source: GOC
    10. organ regeneration Source: RGD
    11. regulation of protein catabolic process Source: RGD

    Keywords - Molecular functioni

    Protease inhibitor, Thiol protease inhibitor

    Protein family/group databases

    MEROPSiI27.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Calpastatin
    Alternative name(s):
    Calpain inhibitor
    Gene namesi
    Name:Cast
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 2

    Organism-specific databases

    RGDi2278. Cast.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: RGD
    2. membrane Source: RGD
    3. nucleus Source: RGD

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi613 – 6131G → A: 2.9-fold increase in the IC(50). 1 Publication
    Mutagenesisi613 – 6131G → FG: Turns CAST from an inhibitor into a substrate. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 713713CalpastatinPRO_0000147635Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei86 – 861N6-acetyllysineBy similarity
    Modified residuei171 – 1711PhosphoserineBy similarity
    Modified residuei281 – 2811PhosphoserineBy similarity
    Modified residuei401 – 4011PhosphoserineBy similarity
    Modified residuei403 – 4031PhosphoserineBy similarity
    Modified residuei410 – 4101PhosphoserineBy similarity
    Modified residuei580 – 5801PhosphoserineBy similarity
    Modified residuei582 – 5821PhosphoserineBy similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PaxDbiP27321.
    PRIDEiP27321.

    PTM databases

    PhosphoSiteiP27321.

    Expressioni

    Gene expression databases

    ArrayExpressiP27321.
    GenevestigatoriP27321.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Capn2Q070095EBI-7441624,EBI-1040438

    Protein-protein interaction databases

    DIPiDIP-44338N.
    IntActiP27321. 1 interaction.
    MINTiMINT-4820577.

    Structurei

    Secondary structure

    1
    713
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi195 – 1995
    Helixi236 – 2383
    Helixi241 – 2477
    Helixi271 – 2744
    Turni275 – 2773
    Helixi573 – 5819
    Helixi616 – 6183
    Helixi621 – 6277
    Helixi652 – 6598

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3BOWX-ray2.40C571-664[»]
    3DF0X-ray2.95C193-278[»]
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP27321.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati208 – 26053Inhibitory domain 1Add
    BLAST
    Repeati341 – 39353Inhibitory domain 2Add
    BLAST
    Repeati451 – 50454Inhibitory domain 3Add
    BLAST
    Repeati588 – 64154Inhibitory domain 4Add
    BLAST

    Domaini

    Each of the four flexible inhibitory domains can inhibit one calcium-bound calpain molecule by occupying both sides of the active site.

    Sequence similaritiesi

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG25116.
    GeneTreeiENSGT00390000002993.
    HOVERGENiHBG000183.
    KOiK04281.
    PhylomeDBiP27321.

    Family and domain databases

    InterProiIPR026998. Calpastatin.
    IPR001259. Prot_inh_calpain.
    [Graphical view]
    PANTHERiPTHR10077. PTHR10077. 1 hit.
    PfamiPF00748. Calpain_inhib. 4 hits.
    [Graphical view]

    Sequences (7)i

    Sequence statusi: Complete.

    This entry describes 7 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P27321-1) [UniParc]FASTAAdd to Basket

    Also known as: A

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSRPGPKPAA SSRPRRGAAA SHTQEHVNEK NIGSSSKPAE KKGSDEVTAS    50
    SAATGTSPRM STTGAKAVKI ESEKSQSSEP PVIHEKKPKG KPKEGSEPQT 100
    LPKHASDTGS KHAHKEKALS RSNEQIVSEK SSESKTKFQD APSADGESVA 150
    GGVTVATASD KVVVKKKEKK SLTPTLPMES TLNKLSDKSG VNAALDDLID 200
    TLGECEDTNK DDPPYTGPVV LDPMDSTYLE ALGIKEGTIP PEYRKLLEKN 250
    EAITGPLPDS PKPMGIDHAI DALSSDFTCS SPTGKQTEKE KSTGESSKAQ 300
    SAGVTRSAVP PQEKKRKVEE EVMNDQALQA LSDSLGTRQP DPQSHLRQAK 350
    QVKEAKAKEE RQEKCGEDED TVPAEYRLKP AKDKDGKPLL PEPEETSKCL 400
    SESELIGELS ADFVQPTYQE KPSMPAAKIK KGVVPDDAVE TLARSLGTRK 450
    EDPEDEKSLV DKVKEKAKEE DHEKLGEKEE TIPPDYRLEI VKDKDGKPLL 500
    PKEAEEQLPP LSDDFLLDAL SQDFSSPANI LSLGFEDAKL SAAVSETVSQ 550
    VPAPSNHTAA PPPGTERRDK ELDDALDELS DSLGQRQPDP DENKPLDDKV 600
    KEKIKAEHSE KLGERDDTIP PEYRHLLDND GKDKPEKPLT KNTEKLGQDQ 650
    DPIDALSEDL DSCPPTTETS QNTTKEKGKK TSSSKASKNE EKTKDSSKKT 700
    EEVPKPKVDE DAT 713
    Length:713
    Mass (Da):77,313
    Last modified:July 24, 2007 - v3
    Checksum:i55505300F59A8DE3
    GO
    Isoform 2 (identifier: P27321-2) [UniParc]FASTAAdd to Basket

    Also known as: B

    The sequence of this isoform differs from the canonical sequence as follows:
         98-135: Missing.

    Show »
    Length:675
    Mass (Da):73,172
    Checksum:iD3514B481F47F5A1
    GO
    Isoform 3 (identifier: P27321-3) [UniParc]FASTAAdd to Basket

    Also known as: C

    The sequence of this isoform differs from the canonical sequence as follows:
         166-188: Missing.

    Show »
    Length:690
    Mass (Da):74,714
    Checksum:i5FB95F6D6FAE3487
    GO
    Isoform 4 (identifier: P27321-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         67-79: Missing.
         98-135: Missing.

    Show »
    Length:662
    Mass (Da):71,769
    Checksum:i184C191B609C0CD3
    GO
    Isoform 5 (identifier: P27321-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         98-135: Missing.
         166-188: Missing.

    Show »
    Length:652
    Mass (Da):70,573
    Checksum:i26A465A95B697D11
    GO
    Isoform 6 (identifier: P27321-6) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         67-79: Missing.
         98-135: Missing.
         166-188: Missing.

    Show »
    Length:639
    Mass (Da):69,170
    Checksum:i777B3D8554E57AE7
    GO
    Isoform 7 (identifier: P27321-7) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-177: Missing.

    Show »
    Length:536
    Mass (Da):58,859
    Checksum:iD9BA9EB299CA6BCB
    GO

    Sequence cautioni

    The sequence CAA40053.1 differs from that shown. Reason: Frameshift at positions 640 and 647.
    The sequence AAK29411.1 differs from that shown. Reason: Erroneous initiation.
    The sequence AAK29412.1 differs from that shown. Reason: Erroneous initiation.
    The sequence CAA40053.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
    The sequence CAA73915.1 differs from that shown. Reason: Erroneous initiation.
    The sequence CAA73916.1 differs from that shown. Reason: Erroneous initiation.
    The sequence CAA73917.1 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti161 – 1611K → E in CAA40053. (PubMed:17570336)Curated
    Sequence conflicti161 – 1611K → E in AAK29411. 1 PublicationCurated
    Sequence conflicti209 – 2091N → S in CAA73917. (PubMed:9475181)Curated
    Sequence conflicti314 – 3141K → E in AAK29412. 1 PublicationCurated
    Sequence conflicti463 – 4631V → G in ABA86879. (PubMed:17570336)Curated
    Sequence conflicti463 – 4631V → G in ABA86880. (PubMed:17570336)Curated
    Sequence conflicti463 – 4631V → G in ABA86881. (PubMed:17570336)Curated
    Sequence conflicti463 – 4631V → G in ABA86882. (PubMed:17570336)Curated
    Sequence conflicti463 – 4631V → G in ABA86883. (PubMed:17570336)Curated
    Sequence conflicti463 – 4631V → G in ABA86884. (PubMed:17570336)Curated
    Sequence conflicti463 – 4631V → G in ABB90254. (PubMed:17570336)Curated
    Sequence conflicti463 – 4631V → G in CAA73916. (PubMed:9475181)Curated
    Sequence conflicti481 – 4811T → A in CAA73917. (PubMed:9475181)Curated
    Sequence conflicti518 – 5181D → G in CAA73917. (PubMed:9475181)Curated
    Sequence conflicti611 – 6111K → R in CAA73915. (PubMed:9475181)Curated
    Sequence conflicti646 – 6461L → P in AAH91239. (PubMed:15489334)Curated
    Sequence conflicti646 – 6461L → P in CAA73915. (PubMed:9475181)Curated
    Sequence conflicti646 – 6461L → P in CAA73917. (PubMed:9475181)Curated
    Sequence conflicti646 – 6461L → P in AAK29411. 1 PublicationCurated
    Sequence conflicti646 – 6461L → P in AAK29412. 1 PublicationCurated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 177177Missing in isoform 7. 1 PublicationVSP_026971Add
    BLAST
    Alternative sequencei67 – 7913Missing in isoform 4 and isoform 6. 2 PublicationsVSP_000753Add
    BLAST
    Alternative sequencei98 – 13538Missing in isoform 2, isoform 4, isoform 5 and isoform 6. 5 PublicationsVSP_000754Add
    BLAST
    Alternative sequencei166 – 18823Missing in isoform 3, isoform 5 and isoform 6. 3 PublicationsVSP_026972Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    DQ186624 mRNA. Translation: ABA86879.1.
    DQ186625 mRNA. Translation: ABA86880.1.
    DQ186626 mRNA. Translation: ABA86881.1.
    DQ186627 mRNA. Translation: ABA86882.1.
    DQ186628 mRNA. Translation: ABA86883.1.
    DQ186629 mRNA. Translation: ABA86884.1.
    DQ287975 mRNA. Translation: ABB90254.1.
    BC091239 mRNA. Translation: AAH91239.1.
    X56729 mRNA. Translation: CAA40053.1. Sequence problems.
    Y13587 mRNA. Translation: CAA73915.1. Different initiation.
    Y13588 mRNA. Translation: CAA73916.1. Different initiation.
    Y13589 mRNA. Translation: CAA73917.1. Different initiation.
    AF346597 mRNA. Translation: AAK29411.1. Different initiation.
    AF346598 mRNA. Translation: AAK29412.1. Different initiation.
    X62520 mRNA. Translation: CAA44386.1.
    PIRiS15074.
    S20611.
    RefSeqiNP_001028887.1. NM_001033715.1.
    NP_001028888.1. NM_001033716.1.
    NP_445747.2. NM_053295.2.
    UniGeneiRn.17481.

    Genome annotation databases

    EnsembliENSRNOT00000062054; ENSRNOP00000058758; ENSRNOG00000010286.
    GeneIDi25403.
    KEGGirno:25403.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    DQ186624 mRNA. Translation: ABA86879.1 .
    DQ186625 mRNA. Translation: ABA86880.1 .
    DQ186626 mRNA. Translation: ABA86881.1 .
    DQ186627 mRNA. Translation: ABA86882.1 .
    DQ186628 mRNA. Translation: ABA86883.1 .
    DQ186629 mRNA. Translation: ABA86884.1 .
    DQ287975 mRNA. Translation: ABB90254.1 .
    BC091239 mRNA. Translation: AAH91239.1 .
    X56729 mRNA. Translation: CAA40053.1 . Sequence problems.
    Y13587 mRNA. Translation: CAA73915.1 . Different initiation.
    Y13588 mRNA. Translation: CAA73916.1 . Different initiation.
    Y13589 mRNA. Translation: CAA73917.1 . Different initiation.
    AF346597 mRNA. Translation: AAK29411.1 . Different initiation.
    AF346598 mRNA. Translation: AAK29412.1 . Different initiation.
    X62520 mRNA. Translation: CAA44386.1 .
    PIRi S15074.
    S20611.
    RefSeqi NP_001028887.1. NM_001033715.1.
    NP_001028888.1. NM_001033716.1.
    NP_445747.2. NM_053295.2.
    UniGenei Rn.17481.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3BOW X-ray 2.40 C 571-664 [» ]
    3DF0 X-ray 2.95 C 193-278 [» ]
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-44338N.
    IntActi P27321. 1 interaction.
    MINTi MINT-4820577.

    Protein family/group databases

    MEROPSi I27.001.

    PTM databases

    PhosphoSitei P27321.

    Proteomic databases

    PaxDbi P27321.
    PRIDEi P27321.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000062054 ; ENSRNOP00000058758 ; ENSRNOG00000010286 .
    GeneIDi 25403.
    KEGGi rno:25403.

    Organism-specific databases

    CTDi 831.
    RGDi 2278. Cast.

    Phylogenomic databases

    eggNOGi NOG25116.
    GeneTreei ENSGT00390000002993.
    HOVERGENi HBG000183.
    KOi K04281.
    PhylomeDBi P27321.

    Miscellaneous databases

    EvolutionaryTracei P27321.
    NextBioi 606501.
    PROi P27321.

    Gene expression databases

    ArrayExpressi P27321.
    Genevestigatori P27321.

    Family and domain databases

    InterProi IPR026998. Calpastatin.
    IPR001259. Prot_inh_calpain.
    [Graphical view ]
    PANTHERi PTHR10077. PTHR10077. 1 hit.
    Pfami PF00748. Calpain_inhib. 4 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Multiple rat brain calpastatin forms are produced by distinct starting points and alternative splicing of the N-terminal exons."
      De Tullio R., Averna M., Stifanese R., Parr T., Bardsley R.G., Pontremoli S., Melloni E.
      Arch. Biochem. Biophys. 465:148-156(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6 AND 7).
      Strain: Sprague-Dawley.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Liver.
    3. "Rat calpastatin has diverged primary sequence from other mammalian calpastatins but retains functionally important sequences."
      Ishida S., Emori Y., Suzuki K.
      Biochim. Biophys. Acta 1088:436-438(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 55-713 (ISOFORM 1).
      Tissue: Liver.
    4. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 55-713 (ISOFORMS 1; 2 AND 5).
      Strain: Sprague-Dawley.
      Tissue: Brain.
    5. "Hypoxic induction of two rat cardiac calpastatin cDNAs."
      Risbood M.P., Lin H., Lee T.
      Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 59-713 (ISOFORMS 1 AND 5).
      Strain: Sprague-Dawley.
      Tissue: Heart.
    6. "Multiple forms of rat calpastatin cDNA in the coding region of functionally unknown amino-terminal domain."
      Lee W.J., Hatanaka M., Maki M.
      Biochim. Biophys. Acta 1129:251-253(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 60-188 (ISOFORMS 1; 2 AND 4).
      Strain: Fischer.
    7. "Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains."
      Moldoveanu T., Gehring K., Green D.R.
      Nature 456:404-408(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 193-278 IN COMPLEX WITH CAPN2 AND CAPNS1.
    8. "Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin."
      Hanna R.A., Campbell R.L., Davies P.L.
      Nature 456:409-412(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 571-664 IN COMPLEX WITH CAPN2 AND CAPNS1, INHIBITORY DOMAINS, MUTAGENESIS OF GLY-613.

    Entry informationi

    Entry nameiICAL_RAT
    AccessioniPrimary (citable) accession number: P27321
    Secondary accession number(s): A5GXY4
    , A5GXY5, A5GXY6, A5GXY7, A5GXY8, A5GXY9, A5GXZ7, O55151, O55152, O55153, Q5BK19, Q99MG1, Q99MG2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: July 24, 2007
    Last modified: October 1, 2014
    This is version 107 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3