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Protein

Calpastatin

Gene

Cast

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

  • cadherin binding Source: RGD
  • calcium-dependent cysteine-type endopeptidase inhibitor activity Source: RGD
  • protease binding Source: RGD
  • RNA binding Source: RGD

GO - Biological processi

  • aging Source: RGD
  • animal organ regeneration Source: RGD
  • brain development Source: RGD
  • egg activation Source: RGD
  • inhibition of cysteine-type endopeptidase activity Source: RGD
  • liver development Source: RGD
  • myoblast differentiation Source: RGD
  • myoblast fusion Source: RGD
  • negative regulation of catalytic activity Source: RGD
  • negative regulation of cell cycle arrest Source: RGD
  • negative regulation of peptidase activity Source: RGD
  • negative regulation of type B pancreatic cell apoptotic process Source: RGD
  • regulation of protein catabolic process Source: RGD

Keywordsi

Molecular functionProtease 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2278 Cast

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi613G → A: 2.9-fold increase in the IC(50). 1 Publication1
Mutagenesisi613G → FG: Turns CAST from an inhibitor into a substrate. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001476351 – 713CalpastatinAdd BLAST713

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei57PhosphoserineCombined sources1
Cross-linki69Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei86N6-acetyllysineBy similarity1
Modified residuei122PhosphoserineCombined sources1
Modified residuei171PhosphoserineCombined sources1
Modified residuei173PhosphothreonineCombined sources1
Modified residuei260PhosphoserineCombined sources1
Modified residuei281PhosphoserineBy similarity1
Modified residuei401PhosphoserineBy similarity1
Modified residuei403PhosphoserineBy similarity1
Modified residuei410PhosphoserineBy similarity1
Modified residuei445PhosphoserineBy similarity1
Modified residuei521PhosphoserineBy similarity1
Modified residuei532PhosphoserineBy similarity1
Modified residuei580PhosphoserineCombined sources1
Modified residuei582PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP27321
PeptideAtlasiP27321
PRIDEiP27321

PTM databases

iPTMnetiP27321
PhosphoSitePlusiP27321

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
Capn2Q0700910EBI-7441624,EBI-1040438

GO - Molecular functioni

  • cadherin binding Source: RGD
  • protease binding Source: RGD

Protein-protein interaction databases

DIPiDIP-44338N
IntActiP27321, 1 interactor
MINTiP27321
STRINGi10116.ENSRNOP00000058759

Structurei

Secondary structure

1713
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi195 – 199Combined sources5
Helixi236 – 238Combined sources3
Helixi241 – 247Combined sources7
Helixi271 – 274Combined sources4
Turni275 – 277Combined sources3
Helixi573 – 581Combined sources9
Helixi616 – 618Combined sources3
Helixi621 – 627Combined sources7
Helixi652 – 659Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BOWX-ray2.40C571-664[»]
3DF0X-ray2.95C193-278[»]
SMRiP27321
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27321

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati208 – 260Inhibitory domain 1Add BLAST53
Repeati341 – 393Inhibitory domain 2Add BLAST53
Repeati451 – 504Inhibitory domain 3Add BLAST54
Repeati588 – 641Inhibitory domain 4Add BLAST54

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

eggNOGiENOG410IFF9 Eukaryota
ENOG4111YF0 LUCA
HOVERGENiHBG000183
InParanoidiP27321
KOiK04281
PhylomeDBiP27321

Family and domain databases

InterProiView protein in InterPro
IPR026998 Calpastatin
IPR001259 Prot_inh_calpain
PANTHERiPTHR10077 PTHR10077, 2 hits
PfamiView protein in Pfam
PF00748 Calpain_inhib, 4 hits

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

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

        10         20         30         40         50
MSRPGPKPAA SSRPRRGAAA SHTQEHVNEK NIGSSSKPAE KKGSDEVTAS
60 70 80 90 100
SAATGTSPRM STTGAKAVKI ESEKSQSSEP PVIHEKKPKG KPKEGSEPQT
110 120 130 140 150
LPKHASDTGS KHAHKEKALS RSNEQIVSEK SSESKTKFQD APSADGESVA
160 170 180 190 200
GGVTVATASD KVVVKKKEKK SLTPTLPMES TLNKLSDKSG VNAALDDLID
210 220 230 240 250
TLGECEDTNK DDPPYTGPVV LDPMDSTYLE ALGIKEGTIP PEYRKLLEKN
260 270 280 290 300
EAITGPLPDS PKPMGIDHAI DALSSDFTCS SPTGKQTEKE KSTGESSKAQ
310 320 330 340 350
SAGVTRSAVP PQEKKRKVEE EVMNDQALQA LSDSLGTRQP DPQSHLRQAK
360 370 380 390 400
QVKEAKAKEE RQEKCGEDED TVPAEYRLKP AKDKDGKPLL PEPEETSKCL
410 420 430 440 450
SESELIGELS ADFVQPTYQE KPSMPAAKIK KGVVPDDAVE TLARSLGTRK
460 470 480 490 500
EDPEDEKSLV DKVKEKAKEE DHEKLGEKEE TIPPDYRLEI VKDKDGKPLL
510 520 530 540 550
PKEAEEQLPP LSDDFLLDAL SQDFSSPANI LSLGFEDAKL SAAVSETVSQ
560 570 580 590 600
VPAPSNHTAA PPPGTERRDK ELDDALDELS DSLGQRQPDP DENKPLDDKV
610 620 630 640 650
KEKIKAEHSE KLGERDDTIP PEYRHLLDND GKDKPEKPLT KNTEKLGQDQ
660 670 680 690 700
DPIDALSEDL DSCPPTTETS QNTTKEKGKK TSSSKASKNE EKTKDSSKKT
710
EEVPKPKVDE DAT
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 AAK29411 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAK29412 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAA40053 differs from that shown. Reason: Frameshift at positions 640 and 647.Curated
The sequence CAA40053 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA73915 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAA73916 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAA73917 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti161K → E in CAA40053 (PubMed:17570336).Curated1
Sequence conflicti161K → E in AAK29411 (Ref. 5) Curated1
Sequence conflicti209N → S in CAA73917 (PubMed:9475181).Curated1
Sequence conflicti314K → E in AAK29412 (Ref. 5) Curated1
Sequence conflicti463V → G in ABA86879 (PubMed:17570336).Curated1
Sequence conflicti463V → G in ABA86880 (PubMed:17570336).Curated1
Sequence conflicti463V → G in ABA86881 (PubMed:17570336).Curated1
Sequence conflicti463V → G in ABA86882 (PubMed:17570336).Curated1
Sequence conflicti463V → G in ABA86883 (PubMed:17570336).Curated1
Sequence conflicti463V → G in ABA86884 (PubMed:17570336).Curated1
Sequence conflicti463V → G in ABB90254 (PubMed:17570336).Curated1
Sequence conflicti463V → G in CAA73916 (PubMed:9475181).Curated1
Sequence conflicti481T → A in CAA73917 (PubMed:9475181).Curated1
Sequence conflicti518D → G in CAA73917 (PubMed:9475181).Curated1
Sequence conflicti611K → R in CAA73915 (PubMed:9475181).Curated1
Sequence conflicti646L → P in AAH91239 (PubMed:15489334).Curated1
Sequence conflicti646L → P in CAA73915 (PubMed:9475181).Curated1
Sequence conflicti646L → P in CAA73917 (PubMed:9475181).Curated1
Sequence conflicti646L → P in AAK29411 (Ref. 5) Curated1
Sequence conflicti646L → P in AAK29412 (Ref. 5) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0269711 – 177Missing in isoform 7. 1 PublicationAdd BLAST177
Alternative sequenceiVSP_00075367 – 79Missing in isoform 4 and isoform 6. 2 PublicationsAdd BLAST13
Alternative sequenceiVSP_00075498 – 135Missing in isoform 2, isoform 4, isoform 5 and isoform 6. 5 PublicationsAdd BLAST38
Alternative sequenceiVSP_026972166 – 188Missing in isoform 3, isoform 5 and isoform 6. 3 PublicationsAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

GeneIDi25403
KEGGirno:25403

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

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 historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: July 24, 2007
Last modified: February 28, 2018
This is version 127 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health