UniProtKB - P20810 (ICAL_HUMAN)
Calpastatin
CAST
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: BHF-UCL
- calcium-dependent cysteine-type endopeptidase inhibitor activity Source: CAFA
- endopeptidase inhibitor activity Source: ProtInc
- RNA binding Source: UniProtKB
GO - Biological processi
- inhibition of cysteine-type endopeptidase activity Source: CAFA
- negative regulation of type B pancreatic cell apoptotic process Source: BHF-UCL
- presynaptic active zone organization Source: ARUK-UCL
Keywordsi
Molecular function | Protease inhibitor, Thiol protease inhibitor |
Enzyme and pathway databases
PathwayCommonsi | P20810 |
Reactomei | R-HSA-1474228, Degradation of the extracellular matrix R-HSA-8862803, Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models |
SignaLinki | P20810 |
SIGNORi | P20810 |
Protein family/group databases
MEROPSi | I27.001 |
Names & Taxonomyi
Protein namesi | Recommended name: CalpastatinAlternative name(s): Calpain inhibitor Sperm BS-17 component |
Gene namesi | Name:CAST |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:1515, CAST |
MIMi | 114090, gene |
neXtProti | NX_P20810 |
VEuPathDBi | HostDB:ENSG00000153113 |
Subcellular locationi
Cytosol
- cytosol Source: BHF-UCL
Endoplasmic reticulum
- endoplasmic reticulum Source: HPA
Other locations
Pathology & Biotechi
Involvement in diseasei
Peeling skin with leukonychia, acral punctate keratoses, cheilitis, and knuckle pads (PLACK)1 Publication
Keywords - Diseasei
Palmoplantar keratodermaOrganism-specific databases
DisGeNETi | 831 |
MalaCardsi | CAST |
MIMi | 616295, phenotype |
OpenTargetsi | ENSG00000153113 |
Orphaneti | 444138, Peeling skin-leukonychia-acral punctate keratoses-cheilitis-knuckle pads syndrome |
PharmGKBi | PA26098 |
Miscellaneous databases
Pharosi | P20810, Tbio |
Chemistry databases
DrugBanki | DB11638, Artenimol DB01373, Calcium |
Genetic variation databases
BioMutai | CAST |
DMDMi | 126302556 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000147632 | 1 – 708 | CalpastatinAdd BLAST | 708 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Cross-linki | 32 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | |||
Modified residuei | 50 | N6-acetyllysineBy similarity | 1 | ||
Modified residuei | 87 | PhosphoserineBy similarity | 1 | ||
Modified residuei | 133 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 135 | PhosphothreonineBy similarity | 1 | ||
Modified residuei | 222 | PhosphoserineBy similarity | 1 | ||
Modified residuei | 243 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 364 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 366 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 373 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 440 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 516 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 527 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 563 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 575 | PhosphoserineCombined sources | 1 | ||
Modified residuei | 577 | PhosphoserineCombined sources | 1 | ||
Isoform 5 (identifier: P20810-5) | |||||
Modified residuei | 11 | PhosphoserineCombined sources | 1 | ||
Isoform 6 (identifier: P20810-6) | |||||
Modified residuei | 11 | PhosphoserineCombined sources | 1 | ||
Isoform 7 (identifier: P20810-7) | |||||
Modified residuei | 11 | PhosphoserineCombined sources | 1 | ||
Isoform 9 (identifier: P20810-9) | |||||
Modified residuei | 11 | PhosphoserineCombined sources | 1 | ||
Isoform 10 (identifier: P20810-10) | |||||
Modified residuei | 11 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
CPTACi | CPTAC-1023 CPTAC-1024 |
EPDi | P20810 |
jPOSTi | P20810 |
MassIVEi | P20810 |
MaxQBi | P20810 |
PeptideAtlasi | P20810 |
PRIDEi | P20810 |
ProteomicsDBi | 33826 33906 53796 [P20810-1] 53797 [P20810-2] 53798 [P20810-3] 53799 [P20810-4] 53800 [P20810-5] 53801 [P20810-6] 53802 [P20810-7] 6573 |
TopDownProteomicsi | P20810-5 [P20810-5] |
PTM databases
GlyGeni | P20810, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P20810 |
MetOSitei | P20810 |
PhosphoSitePlusi | P20810 |
Expressioni
Gene expression databases
Bgeei | ENSG00000153113, Expressed in calcaneal tendon and 251 other tissues |
ExpressionAtlasi | P20810, baseline and differential |
Genevisiblei | P20810, HS |
Organism-specific databases
HPAi | ENSG00000153113, Low tissue specificity |
Interactioni
Binary interactionsi
P20810
With | #Exp. | IntAct |
---|---|---|
NCK1 [P16333] | 2 | EBI-1268770,EBI-389883 |
CACNA1C [O35505] from Cavia porcellus. | 2 | EBI-1268770,EBI-9084208 |
GO - Molecular functioni
- cadherin binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 107281, 64 interactors |
IntActi | P20810, 30 interactors |
MINTi | P20810 |
STRINGi | 9606.ENSP00000379157 |
Miscellaneous databases
RNActi | P20810, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 170 – 222 | Inhibitory domain 1Add BLAST | 53 | |
Repeati | 304 – 356 | Inhibitory domain 2Add BLAST | 53 | |
Repeati | 446 – 499 | Inhibitory domain 3Add BLAST | 54 | |
Repeati | 583 – 636 | Inhibitory domain 4Add BLAST | 54 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 187 | DisorderedSequence analysisAdd BLAST | 187 | |
Regioni | 212 – 404 | DisorderedSequence analysisAdd BLAST | 193 | |
Regioni | 416 – 527 | DisorderedSequence analysisAdd BLAST | 112 | |
Regioni | 543 – 708 | DisorderedSequence analysisAdd BLAST | 166 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 32 – 66 | Basic and acidic residuesSequence analysisAdd BLAST | 35 | |
Compositional biasi | 67 – 92 | Polar residuesSequence analysisAdd BLAST | 26 | |
Compositional biasi | 170 – 185 | Polar residuesSequence analysisAdd BLAST | 16 | |
Compositional biasi | 273 – 287 | Basic and acidic residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 306 – 394 | Basic and acidic residuesSequence analysisAdd BLAST | 89 | |
Compositional biasi | 437 – 497 | Basic and acidic residuesSequence analysisAdd BLAST | 61 | |
Compositional biasi | 543 – 559 | Polar residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 561 – 650 | Basic and acidic residuesSequence analysisAdd BLAST | 90 | |
Compositional biasi | 690 – 708 | Basic and acidic residuesSequence analysisAdd BLAST | 19 |
Domaini
Sequence similaritiesi
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | ENOG502RHIZ, Eukaryota |
GeneTreei | ENSGT00390000002993 |
InParanoidi | P20810 |
OMAi | IKEKDHT |
OrthoDBi | 203890at2759 |
PhylomeDBi | P20810 |
TreeFami | TF332525 |
Family and domain databases
DisProti | DP00196 |
InterProi | View protein in InterPro IPR026998, Calpastatin IPR001259, Prot_inh_calpain |
PANTHERi | PTHR10077, PTHR10077, 1 hit |
Pfami | View protein in Pfam PF00748, Calpain_inhib, 4 hits |
s (10+)i Sequence
Sequence statusi: Complete.
This entry describes 10 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 10 described isoforms and 33 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MNPTETKAIP VSQQMEGPHL PNKKKHKKQA VKTEPEKKSQ STKLSVVHEK
60 70 80 90 100
KSQEGKPKEH TEPKSLPKQA SDTGSNDAHN KKAVSRSAEQ QPSEKSTEPK
110 120 130 140 150
TKPQDMISAG GESVAGITAI SGKPGDKKKE KKSLTPAVPV ESKPDKPSGK
160 170 180 190 200
SGMDAALDDL IDTLGGPEET EEENTTYTGP EVSDPMSSTY IEELGKREVT
210 220 230 240 250
IPPKYRELLA KKEGITGPPA DSSKPIGPDD AIDALSSDFT CGSPTAAGKK
260 270 280 290 300
TEKEESTEVL KAQSAGTVRS AAPPQEKKRK VEKDTMSDQA LEALSASLGT
310 320 330 340 350
RQAEPELDLR SIKEVDEAKA KEEKLEKCGE DDETIPSEYR LKPATDKDGK
360 370 380 390 400
PLLPEPEEKP KPRSESELID ELSEDFDRSE CKEKPSKPTE KTEESKAAAP
410 420 430 440 450
APVSEAVCRT SMCSIQSAPP EPATLKGTVP DDAVEALADS LGKKEADPED
460 470 480 490 500
GKPVMDKVKE KAKEEDREKL GEKEETIPPD YRLEEVKDKD GKPLLPKESK
510 520 530 540 550
EQLPPMSEDF LLDALSEDFS GPQNASSLKF EDAKLAAAIS EVVSQTPAST
560 570 580 590 600
TQAGAPPRDT SQSDKDLDDA LDKLSDSLGQ RQPDPDENKP MEDKVKEKAK
610 620 630 640 650
AEHRDKLGER DDTIPPEYRH LLDDNGQDKP VKPPTKKSED SKKPADDQDP
660 670 680 690 700
IDALSGDLDS CPSTTETSQN TAKDKCKKAA SSSKAPKNGG KAKDSAKTTE
ETSKPKDD
The sequence of this isoform differs from the canonical sequence as follows:
1-29: MNPTETKAIPVSQQMEGPHLPNKKKHKKQ → MSQPGQKPAA...SSSMNPTETK
Computationally mapped potential isoform sequencesi
There are 33 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PCH5 | E9PCH5_HUMAN | Calpastatin | CAST | 673 | Annotation score: | ||
E9PDE4 | E9PDE4_HUMAN | Calpastatin | CAST | 636 | Annotation score: | ||
A0A0C4DGB5 | A0A0C4DGB5_HUMAN | Calpastatin | CAST | 741 | Annotation score: | ||
F8W7E0 | F8W7E0_HUMAN | Calpastatin | CAST | 393 | Annotation score: | ||
E7ES10 | E7ES10_HUMAN | Calpastatin | CAST | 642 | Annotation score: | ||
E7EVY3 | E7EVY3_HUMAN | Calpastatin | CAST | 693 | Annotation score: | ||
H0YA91 | H0YA91_HUMAN | Calpastatin | CAST | 301 | Annotation score: | ||
B7Z574 | B7Z574_HUMAN | Calpastatin | CAST | 694 | Annotation score: | ||
E7EQ12 | E7EQ12_HUMAN | Calpastatin | CAST | 423 | Annotation score: | ||
E7EQA0 | E7EQA0_HUMAN | Calpastatin | CAST | 431 | Annotation score: | ||
There are more potential isoformsShow all |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 467 | R → L in AAC50136 (Ref. 12) Curated | 1 | |
Sequence conflicti | 486 – 488 | VKD → GKE in AAC50136 (Ref. 12) Curated | 3 | |
Sequence conflicti | 543 | V → L in AAC50136 (Ref. 12) Curated | 1 | |
Sequence conflicti | 562 | Missing in AAB60371 (Ref. 15) Curated | 1 | |
Sequence conflicti | 651 | I → V in AAD09102 (Ref. 16) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_030741 | 380 | E → K. Corresponds to variant dbSNP:rs1643702Ensembl. | 1 | |
Natural variantiVAR_022686 | 408 | C → S4 PublicationsCorresponds to variant dbSNP:rs754615Ensembl. | 1 | |
Natural variantiVAR_030742 | 537 | A → V. Corresponds to variant dbSNP:rs4948Ensembl. | 1 | |
Natural variantiVAR_005298 | 592 | E → G1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_000741 | 1 – 105 | Missing in isoform 3. 1 PublicationAdd BLAST | 105 | |
Alternative sequenceiVSP_047393 | 1 – 62 | MNPTE…KEHTE → MSQPGQKPAASPRPRRAAAA RRTHEHVSEKTSESPSKPGE KKGSDEKKAASLGSSQSSRT YAGGTASATKVSASSGATSK SSSMNPTETKAVKTEPEKKS QSTK in isoform 9. CuratedAdd BLAST | 62 | |
Alternative sequenceiVSP_038037 | 1 – 29 | MNPTE…KHKKQ → MSQPGQKPAASPRPRRAAAA RRTHEHVSEKTSESPSKPGE KKGSDEKKAASLGSSQSSRT YAGGTASATKVSASSGATSK SSSMNPTETK in isoform 5 and isoform 10. 2 PublicationsAdd BLAST | 29 | |
Alternative sequenceiVSP_038038 | 1 | M → MSQPGQKPAASPRPRRAAAA RRTHEHVSEKTSESPSKPGE KKGSDEKKAASLGSSQSSRT YAGGTASATKVSASSGATSK SSSM in isoform 6 and isoform 7. Curated | 1 | |
Alternative sequenceiVSP_000742 | 9 – 30 | Missing in isoform 4 and isoform 8. 3 PublicationsAdd BLAST | 22 | |
Alternative sequenceiVSP_000743 | 44 – 62 | Missing in isoform 4 and isoform 7. 2 PublicationsAdd BLAST | 19 | |
Alternative sequenceiVSP_000744 | 212 – 224 | Missing in isoform 2, isoform 3 and isoform 5. 2 PublicationsAdd BLAST | 13 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
AlphaFoldDBi | P20810 |
SMRi | P20810 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 107281, 64 interactors |
IntActi | P20810, 30 interactors |
MINTi | P20810 |
STRINGi | 9606.ENSP00000379157 |
Chemistry databases
DrugBanki | DB11638, Artenimol DB01373, Calcium |
Protein family/group databases
MEROPSi | I27.001 |
PTM databases
GlyGeni | P20810, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P20810 |
MetOSitei | P20810 |
PhosphoSitePlusi | P20810 |
Genetic variation databases
BioMutai | CAST |
DMDMi | 126302556 |
Proteomic databases
CPTACi | CPTAC-1023 CPTAC-1024 |
EPDi | P20810 |
jPOSTi | P20810 |
MassIVEi | P20810 |
MaxQBi | P20810 |
PeptideAtlasi | P20810 |
PRIDEi | P20810 |
ProteomicsDBi | 33826 33906 53796 [P20810-1] 53797 [P20810-2] 53798 [P20810-3] 53799 [P20810-4] 53800 [P20810-5] 53801 [P20810-6] 53802 [P20810-7] 6573 |
TopDownProteomicsi | P20810-5 [P20810-5] |
Protocols and materials databases
Antibodypediai | 4008, 410 antibodies from 32 providers |
DNASUi | 831 |
Genome annotation databases
Organism-specific databases
CTDi | 831 |
DisGeNETi | 831 |
GeneCardsi | CAST |
HGNCi | HGNC:1515, CAST |
HPAi | ENSG00000153113, Low tissue specificity |
MalaCardsi | CAST |
MIMi | 114090, gene 616295, phenotype |
neXtProti | NX_P20810 |
OpenTargetsi | ENSG00000153113 |
Orphaneti | 444138, Peeling skin-leukonychia-acral punctate keratoses-cheilitis-knuckle pads syndrome |
PharmGKBi | PA26098 |
VEuPathDBi | HostDB:ENSG00000153113 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RHIZ, Eukaryota |
GeneTreei | ENSGT00390000002993 |
InParanoidi | P20810 |
OMAi | IKEKDHT |
OrthoDBi | 203890at2759 |
PhylomeDBi | P20810 |
TreeFami | TF332525 |
Enzyme and pathway databases
PathwayCommonsi | P20810 |
Reactomei | R-HSA-1474228, Degradation of the extracellular matrix R-HSA-8862803, Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models |
SignaLinki | P20810 |
SIGNORi | P20810 |
Miscellaneous databases
BioGRID-ORCSi | 831, 20 hits in 1082 CRISPR screens |
ChiTaRSi | CAST, human |
GeneWikii | Calpastatin |
GenomeRNAii | 831 |
Pharosi | P20810, Tbio |
PROi | PR:P20810 |
RNActi | P20810, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000153113, Expressed in calcaneal tendon and 251 other tissues |
ExpressionAtlasi | P20810, baseline and differential |
Genevisiblei | P20810, HS |
Family and domain databases
DisProti | DP00196 |
InterProi | View protein in InterPro IPR026998, Calpastatin IPR001259, Prot_inh_calpain |
PANTHERi | PTHR10077, PTHR10077, 1 hit |
Pfami | View protein in Pfam PF00748, Calpain_inhib, 4 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | ICAL_HUMAN | |
Accessioni | P20810Primary (citable) accession number: P20810 Secondary accession number(s): B7Z468 Q9H1Z5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1991 |
Last sequence update: | February 20, 2007 | |
Last modified: | May 25, 2022 | |
This is version 198 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families