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P27321

- ICAL_RAT

UniProt

P27321 - ICAL_RAT

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Protein

Calpastatin

Gene
Cast
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 4 out of 5 - Experimental evidence at protein leveli

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. cysteine-type endopeptidase inhibitor activity Source: UniProtKB-KW
  2. protein binding Source: IntAct
Complete GO annotation...

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.

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-acetyllysine By similarity
Modified residuei171 – 1711Phosphoserine By similarity
Modified residuei281 – 2811Phosphoserine By similarity
Modified residuei401 – 4011Phosphoserine By similarity
Modified residuei403 – 4031Phosphoserine By similarity
Modified residuei410 – 4101Phosphoserine By similarity
Modified residuei580 – 5801Phosphoserine By similarity
Modified residuei582 – 5821Phosphoserine By 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[»]

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.1 Publication

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.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 177177Missing in isoform 7. VSP_026971Add
BLAST
Alternative sequencei67 – 7913Missing in isoform 4 and isoform 6. VSP_000753Add
BLAST
Alternative sequencei98 – 13538Missing in isoform 2, isoform 4, isoform 5 and isoform 6. VSP_000754Add
BLAST
Alternative sequencei166 – 18823Missing in isoform 3, isoform 5 and isoform 6. VSP_026972Add
BLAST

Sequence conflict

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

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

« Hide 'large scale' publications
  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: June 11, 2014
This is version 106 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

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