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P27321 (ICAL_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calpastatin
Alternative name(s):
Calpain inhibitor
Gene names
Name:Cast
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length713 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Domain

Each of the four flexible inhibitory domains can inhibit one calcium-bound calpain molecule by occupying both sides of the active site. Ref.8

Sequence similarities

Belongs to the protease inhibitor I27 (calpastatin) family. [View classification]

Sequence caution

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 CAA40053.1 differs from that shown. Reason: Frameshift at positions 640 and 647.

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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Capn2Q070095EBI-7441624,EBI-1040438

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P27321-1)

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.
Isoform 2 (identifier: P27321-2)

Also known as: B;

The sequence of this isoform differs from the canonical sequence as follows:
     98-135: Missing.
Isoform 3 (identifier: P27321-3)

Also known as: C;

The sequence of this isoform differs from the canonical sequence as follows:
     166-188: Missing.
Isoform 4 (identifier: P27321-4)

The sequence of this isoform differs from the canonical sequence as follows:
     67-79: Missing.
     98-135: Missing.
Isoform 5 (identifier: P27321-5)

The sequence of this isoform differs from the canonical sequence as follows:
     98-135: Missing.
     166-188: Missing.
Isoform 6 (identifier: P27321-6)

The sequence of this isoform differs from the canonical sequence as follows:
     67-79: Missing.
     98-135: Missing.
     166-188: Missing.
Isoform 7 (identifier: P27321-7)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 713713Calpastatin
PRO_0000147635

Regions

Repeat208 – 26053Inhibitory domain 1
Repeat341 – 39353Inhibitory domain 2
Repeat451 – 50454Inhibitory domain 3
Repeat588 – 64154Inhibitory domain 4

Amino acid modifications

Modified residue861N6-acetyllysine By similarity
Modified residue1711Phosphoserine By similarity
Modified residue2811Phosphoserine By similarity
Modified residue4011Phosphoserine By similarity
Modified residue4031Phosphoserine By similarity
Modified residue4101Phosphoserine By similarity
Modified residue5801Phosphoserine By similarity
Modified residue5821Phosphoserine By similarity

Natural variations

Alternative sequence1 – 177177Missing in isoform 7.
VSP_026971
Alternative sequence67 – 7913Missing in isoform 4 and isoform 6.
VSP_000753
Alternative sequence98 – 13538Missing in isoform 2, isoform 4, isoform 5 and isoform 6.
VSP_000754
Alternative sequence166 – 18823Missing in isoform 3, isoform 5 and isoform 6.
VSP_026972

Experimental info

Mutagenesis6131G → A: 2.9-fold increase in the IC(50). Ref.8
Mutagenesis6131G → FG: Turns CAST from an inhibitor into a substrate. Ref.8
Sequence conflict1611K → E in CAA40053. Ref.1
Sequence conflict1611K → E in AAK29411. Ref.5
Sequence conflict2091N → S in CAA73917. Ref.4
Sequence conflict3141K → E in AAK29412. Ref.5
Sequence conflict4631V → G in ABA86879. Ref.1
Sequence conflict4631V → G in ABA86880. Ref.1
Sequence conflict4631V → G in ABA86881. Ref.1
Sequence conflict4631V → G in ABA86882. Ref.1
Sequence conflict4631V → G in ABA86883. Ref.1
Sequence conflict4631V → G in ABA86884. Ref.1
Sequence conflict4631V → G in ABB90254. Ref.1
Sequence conflict4631V → G in CAA73916. Ref.4
Sequence conflict4811T → A in CAA73917. Ref.4
Sequence conflict5181D → G in CAA73917. Ref.4
Sequence conflict6111K → R in CAA73915. Ref.4
Sequence conflict6461L → P in AAH91239. Ref.2
Sequence conflict6461L → P in CAA73915. Ref.4
Sequence conflict6461L → P in CAA73917. Ref.4
Sequence conflict6461L → P in AAK29411. Ref.5
Sequence conflict6461L → P in AAK29412. Ref.5

Secondary structure

.................. 713
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (A) [UniParc].

Last modified July 24, 2007. Version 3.
Checksum: 55505300F59A8DE3

FASTA71377,313
        10         20         30         40         50         60 
MSRPGPKPAA SSRPRRGAAA SHTQEHVNEK NIGSSSKPAE KKGSDEVTAS SAATGTSPRM 

        70         80         90        100        110        120 
STTGAKAVKI ESEKSQSSEP PVIHEKKPKG KPKEGSEPQT LPKHASDTGS KHAHKEKALS 

       130        140        150        160        170        180 
RSNEQIVSEK SSESKTKFQD APSADGESVA GGVTVATASD KVVVKKKEKK SLTPTLPMES 

       190        200        210        220        230        240 
TLNKLSDKSG VNAALDDLID TLGECEDTNK DDPPYTGPVV LDPMDSTYLE ALGIKEGTIP 

       250        260        270        280        290        300 
PEYRKLLEKN EAITGPLPDS PKPMGIDHAI DALSSDFTCS SPTGKQTEKE KSTGESSKAQ 

       310        320        330        340        350        360 
SAGVTRSAVP PQEKKRKVEE EVMNDQALQA LSDSLGTRQP DPQSHLRQAK QVKEAKAKEE 

       370        380        390        400        410        420 
RQEKCGEDED TVPAEYRLKP AKDKDGKPLL PEPEETSKCL SESELIGELS ADFVQPTYQE 

       430        440        450        460        470        480 
KPSMPAAKIK KGVVPDDAVE TLARSLGTRK EDPEDEKSLV DKVKEKAKEE DHEKLGEKEE 

       490        500        510        520        530        540 
TIPPDYRLEI VKDKDGKPLL PKEAEEQLPP LSDDFLLDAL SQDFSSPANI LSLGFEDAKL 

       550        560        570        580        590        600 
SAAVSETVSQ VPAPSNHTAA PPPGTERRDK ELDDALDELS DSLGQRQPDP DENKPLDDKV 

       610        620        630        640        650        660 
KEKIKAEHSE KLGERDDTIP PEYRHLLDND GKDKPEKPLT KNTEKLGQDQ DPIDALSEDL 

       670        680        690        700        710 
DSCPPTTETS QNTTKEKGKK TSSSKASKNE EKTKDSSKKT EEVPKPKVDE DAT 

« Hide

Isoform 2 (B) [UniParc].

Checksum: D3514B481F47F5A1
Show »

FASTA67573,172
Isoform 3 (C) [UniParc].

Checksum: 5FB95F6D6FAE3487
Show »

FASTA69074,714
Isoform 4 [UniParc].

Checksum: 184C191B609C0CD3
Show »

FASTA66271,769
Isoform 5 [UniParc].

Checksum: 26A465A95B697D11
Show »

FASTA65270,573
Isoform 6 [UniParc].

Checksum: 777B3D8554E57AE7
Show »

FASTA63969,170
Isoform 7 [UniParc].

Checksum: D9BA9EB299CA6BCB
Show »

FASTA53658,859

References

« Hide 'large scale' references
[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]"Rat brain contains multiple mRNAs for calpastatin."
De Tullio R., Sparatore B., Salamino F., Melloni E., Pontremoli S.
FEBS Lett. 422:113-117(1998) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS15074.
S20611.
RefSeqNP_001028887.1. NM_001033715.1.
NP_001028888.1. NM_001033716.1.
NP_445747.2. NM_053295.2.
UniGeneRn.17481.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3BOWX-ray2.40C571-664[»]
3DF0X-ray2.95C193-278[»]
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-44338N.
IntActP27321. 1 interaction.
MINTMINT-4820577.

Protein family/group databases

MEROPSI27.001.

PTM databases

PhosphoSiteP27321.

Proteomic databases

PaxDbP27321.
PRIDEP27321.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000062054; ENSRNOP00000058758; ENSRNOG00000010286.
GeneID25403.
KEGGrno:25403.

Organism-specific databases

CTD831.
RGD2278. Cast.

Phylogenomic databases

eggNOGNOG25116.
GeneTreeENSGT00390000002993.
HOVERGENHBG000183.
KOK04281.
PhylomeDBP27321.

Gene expression databases

ArrayExpressP27321.
GenevestigatorP27321.

Family and domain databases

InterProIPR026998. Calpastatin.
IPR001259. Prot_inh_calpain.
[Graphical view]
PANTHERPTHR10077. PTHR10077. 1 hit.
PfamPF00748. Calpain_inhib. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP27321.
NextBio606501.
PROP27321.

Entry information

Entry nameICAL_RAT
AccessionPrimary (citable) accession number: P27321
Secondary accession number(s): A5GXY4 expand/collapse secondary AC list , A5GXY5, A5GXY6, A5GXY7, A5GXY8, A5GXY9, A5GXZ7, O55151, O55152, O55153, Q5BK19, Q99MG1, Q99MG2
Entry history
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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references