Property Summary

NCBI Gene PubMed Count 94
PubMed Score 761.99
PubTator Score 226.16

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (9)

Disease log2 FC p
Multiple myeloma 1.263 6.0e-03
malignant mesothelioma -1.200 8.4e-07
esophageal adenocarcinoma -1.300 4.4e-02
astrocytoma 1.400 2.5e-02
glioblastoma 1.800 6.4e-03
primary pancreatic ductal adenocarcinoma 1.415 2.1e-02
lung cancer -1.700 3.0e-04
lung adenocarcinoma -1.700 3.9e-11
pancreatic cancer 1.100 8.8e-03

Protein-protein Interaction (1)

Gene RIF (43)

PMID Text
25683118 We describe PLACK syndrome, as a clinical entity of defective epidermal adhesion, caused by loss-of-function mutations in calpastatin.
25648699 Loss of CAST in angiogenic ECs facilitates mu-calpain-induced SOCS3 degradation, which amplifies pathological angiogenesis through interleukin-6/STAT3/VEGF-C axis.
24462690 Calpastatin binds with Cav1.2 amino acid motifs in a calcium dependent manner.
23951044 Calpastatin gene (CAST) is not associated with late onset sporadic Parkinson's disease in the Han Chinese population.
23707532 HER2 inhibited calpain-1 activity through upregulating calpastatin, an endogenous calpain inhibitor.
23449483 Linkage analysis and genetic association support involvement of CAST gene in the genetic susceptibility to keratoconus.
23140395 The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression
22572592 Calpastatin overexpression reduces calpain-mediated proteolysis and behavioral impairment after traumatic brain injury.
22288381 Mycoplasma hyorhinis membrane lipoproteins induce calpastatin upregulation in human cells
22206846 Neuronal overexpression of calpastatin modulates amyloid precursor protein processing in brains of transgenic beta-amyloid depositing mice.
22046434 calpastatin-calpain balance varied during Th-1,2, and -17 development; overexpression of a domain of calpastatin suppressed production of IL-6 and IL-17 by Th cells and of IL-6 by fibroblasts; suppression of IL-6 occurred by reducing NF-kappaB signaling
21983488 calpain basal activity becomes measurable at a significant extent in peripheral blood mononuclear cells from cystic fibrosis patients due to a 40-60% decrease in both calpastatin protein and inhibitory activity
21937422 CSL competes with CaM as a partial agonist for the site in the IQ domain in the C-terminal region of the Cav1.2 channel, which may be involved in activation of the channel.
21839844 intervertebral discs at early stages of degeneration expressed low levels of calpastatin, and few cells expressed degenerative enzymes. At more advanced stages of degeneration, expression and number of cells immunopositive for calpastatin were higher
21531560 The data supports the hypothesis that calpastatin may play a role in regulating the initial metastatic dissemination of breast cancer.
21424381 Variations in CAST gene is associated with femoral neck Low bone mineral density.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20127884 A confirmation study reports that a single nucleotide polymorphism and CAST are associated with Parkinson disease.
19913121 Observational study of gene-disease association. (HuGE Navigator)
19756344 Overexpression of calpain-2 and low expression of calpastatin may involve in the pathological development of stress urinary incontinence.
19365859 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
19103264 recruitment of calpastatin into aggregates allows translocation and activation of protease to the membranes; on the contrary, the presence of large amounts of calpastatin in the cytosol prevents both processes, protecting the cell from proteolysis
18809371 Role of the calpain-calpastatin system in the density-dependent growth arrest.
18793761 Proof of concept that the calpastatin-based reagents may be useful to selectively detect the active conformation of calpain.
18724972 Observational study of gene-disease association. (HuGE Navigator)
18544539 c-Myc regulates calpain activity through calpastatin; apoptosis induced by calpain inhibition is dependent on c-Myc, and calpastatin knockdown promotes transformation in c-Myc-negative cells
18537264 performed a full NMR assignment of hCSD1 to characterize it in its solution state
18519038 NMR data of calapastin tripartite binding mode to capain induced by calcium were presented.
18498295 genetically determined IL-1alpha levels may modulate transcription of calpain and calpastatin
18340456 Results suggest a regulation on the calpain-calpastatin expression response to muscle damaging eccentric exercise, but not concentric exercise.
18195134 Genome-wide association study of gene-disease association and pharmacogenomic / toxicogenomic. (HuGE Navigator)
18165173 The activity of calpain in human peripheral blood lymphocytes, was estimated by assessing the levels of limited proteolysis of calpastatin.
17950697 CS(L) modulates Ca2+-channel activity through interacting with the calmodulin-binding site on the C-terminal tail of the Cav1.2 channel.
17137217 Observational study of gene-disease association. (HuGE Navigator)
15950654 A complete calpain-calpastatin system is expressed in the human oocyte and may play a role in the various calcium-mediated processes occurring during activation of human oocytes.
15014085 Overexpression of calpastatin in transgenic mice is associated with an increase in GLUT4 protein.
14992597 Calpastatin amino acid side chains at leucine-11 and isoleucine-18 interact with hydrophobic pockets in calpain, and each of these interactions is indispensable for effective inhibition of calpain.
14612448 calpastatin and calpain-1 represent critical proximal elements in a cascade of pro-apoptotic events leading to Bax, mitochondria, and caspase-3 activation
14559243 insights into how the calpain/calpastatin network is spatially and temporally regulated in cells binding to the extracellular matrix
12482888 Overexpression of calpastatin reduced muscle atrophy during 10 day unloading period. Overexpression completely prevented shift in myofibrillar myosin content from slow to fast isoforms, which normally occurs in muscle unloading.
11849768 Observational study of gene-disease association. (HuGE Navigator)
11849768 involved in the proteolysis of amyloid precursor protein, which is thought to be abnormal in patients with Alzheimer's disease

AA Sequence

MNPTETKAIPVSQQMEGPHLPNKKKHKKQAVKTEPEKKSQSTKLSVVHEKKSQEGKPKEHTEPKSLPKQA      1 - 70
SDTGSNDAHNKKAVSRSAEQQPSEKSTEPKTKPQDMISAGGESVAGITAISGKPGDKKKEKKSLTPAVPV     71 - 140
ESKPDKPSGKSGMDAALDDLIDTLGGPEETEEENTTYTGPEVSDPMSSTYIEELGKREVTIPPKYRELLA    141 - 210
KKEGITGPPADSSKPIGPDDAIDALSSDFTCGSPTAAGKKTEKEESTEVLKAQSAGTVRSAAPPQEKKRK    211 - 280
VEKDTMSDQALEALSASLGTRQAEPELDLRSIKEVDEAKAKEEKLEKCGEDDETIPSEYRLKPATDKDGK    281 - 350
PLLPEPEEKPKPRSESELIDELSEDFDRSECKEKPSKPTEKTEESKAAAPAPVSEAVCRTSMCSIQSAPP    351 - 420
EPATLKGTVPDDAVEALADSLGKKEADPEDGKPVMDKVKEKAKEEDREKLGEKEETIPPDYRLEEVKDKD    421 - 490
GKPLLPKESKEQLPPMSEDFLLDALSEDFSGPQNASSLKFEDAKLAAAISEVVSQTPASTTQAGAPPRDT    491 - 560
SQSDKDLDDALDKLSDSLGQRQPDPDENKPMEDKVKEKAKAEHRDKLGERDDTIPPEYRHLLDDNGQDKP    561 - 630
VKPPTKKSEDSKKPADDQDPIDALSGDLDSCPSTTETSQNTAKDKCKKAASSSKAPKNGGKAKDSAKTTE    631 - 700
ETSKPKDD                                                                  701 - 708
//

Text Mined References (103)

PMID Year Title
25683118 2015 Loss-of-function mutations in CAST cause peeling skin, leukonychia, acral punctate keratoses, cheilitis, and knuckle pads.
25648699 2015 Calpastatin counteracts pathological angiogenesis by inhibiting suppressor of cytokine signaling 3 degradation in vascular endothelial cells.
25468996 2014 E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
25218447 2014 Uncovering global SUMOylation signaling networks in a site-specific manner.
24462690 2014 The Ca(2+)-dependent interaction of calpastatin domain L with the C-terminal tail of the Cav1.2 channel.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23951044 2013 Calpastatin gene (CAST) is not associated with late onset sporadic Parkinson's disease in the Han Chinese population.
23773963 2013 Calpastatin is upregulated in non-immune neuronal cells via toll-like receptor 2 (TLR2) pathways by lipid-containing agonists.
23707532 2013 HER2 regulates Brk/PTK6 stability via upregulating calpastatin, an inhibitor of calpain.
23684705 2013 Modulation by Syk of Bcl-2, calcium and the calpain-calpastatin proteolytic system in human breast cancer cells.
23449483 2013 An association between the calpastatin (CAST) gene and keratoconus.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23140395 2012 Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla.
22658674 2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
22572592 2012 Calpastatin overexpression limits calpain-mediated proteolysis and behavioral deficits following traumatic brain injury.
22288381 2012 Calpastatin upregulation in Mycoplasma hyorhinis-infected cells is promoted by the mycoplasma lipoproteins via the NF-?B pathway.
22286212 2012 Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups.
22206846 2012 Calpastatin modulates APP processing in the brains of ?-amyloid depositing but not wild-type mice.
22046434 2011 Overexpression of a minimal domain of calpastatin suppresses IL-6 production and Th17 development via reduced NF-?B and increased STAT5 signals.
21983488 2011 Evidence for alteration of calpain/calpastatin system in PBMC of cystic fibrosis patients.
21937422 2011 Calpastatin domain L is a partial agonist of the calmodulin-binding site for channel activation in Cav1.2 Ca2+ channels.
21839844 2011 Abundance of calpain and aggrecan-cleavage products of calpain in degenerated human intervertebral discs.
21531560 2011 Calpastatin is associated with lymphovascular invasion in breast cancer.
21424381 2011 Identification of QTL genes for BMD variation using both linkage and gene-based association approaches.
21269460 2011 Initial characterization of the human central proteome.
20953190 2010 A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20127884 2010 SNPs in CAST are associated with Parkinson disease: a confirmation study.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19756344 2010 The role of calpain-calpastatin system in the development of stress urinary incontinence.
19581569 2009 Genome-wide association study of alcohol dependence.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19365859 2009 A novel haplotype-sharing approach for genome-wide case-control association studies implicates the calpastatin gene in Parkinson's disease.
19103264 2009 Involvement of exon 6-mediated calpastatin intracellular movements in the modulation of calpain activation.
19020623 2008 Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin.
19020622 2008 Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains.
18809371 2008 Role of the calpain-calpastatin system in the density-dependent growth arrest.
18793761 2008 Detecting the active conformation of calpain with calpastatin-based reagents.
18724972 2008 Sex differences in environmental and genetic factors for hypertension.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18544539 2008 Regulation of calpain activity by c-Myc through calpastatin and promotion of transformation in c-Myc-negative cells by calpastatin suppression.
18537264 2008 Local structural preferences of calpastatin, the intrinsically unstructured protein inhibitor of calpain.
18519038 2008 Calcium-induced tripartite binding of intrinsically disordered calpastatin to its cognate enzyme, calpain.
18498295 2008 Complex effects of IL1A polymorphism and calpain inhibitors on interleukin 1 alpha (IL-1 alpha) mRNA levels and secretion of IL-1 alpha protein.
18340456 2008 Effects of concentric and repeated eccentric exercise on muscle damage and calpain-calpastatin gene expression in human skeletal muscle.
18195134 2008 Genome-wide pharmacogenomic analysis of the response to interferon beta therapy in multiple sclerosis.
18165173 2007 Ex vivo measurement of calpain activation in human peripheral blood lymphocytes by detection of immunoreactive products of calpastatin degradation.
17974005 2007 The full-ORF clone resource of the German cDNA Consortium.
17950697 2007 Calpastatin binds to a calmodulin-binding site of cardiac Cav1.2 Ca2+ channels.
17474147 2007 Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening.
17137217 2006 Association of sixty-one non-synonymous polymorphisms in forty-one hypertension candidate genes with blood pressure variation and hypertension.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16381901 2006 The LIFEdb database in 2006.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15950654 2005 Expression and immunolocalization of the calpain-calpastatin system in the human oocyte.
15820218 2005 Four promoters direct expression of the calpastatin gene.
15489336 2004 From ORFeome to biology: a functional genomics pipeline.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15372022 2004 The DNA sequence and comparative analysis of human chromosome 5.
15302935 2004 Large-scale characterization of HeLa cell nuclear phosphoproteins.
15044459 2004 RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets.
15014085 2004 Calpain system regulates muscle mass and glucose transporter GLUT4 turnover.
14992597 2004 The beta- and gamma-CH2 of B27-WT's Leu11 and Ile18 side chains play a direct role in calpain inhibition.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14685690 2003 Changes in calpastatin localization and expression during calpain activation: a new mechanism for the regulation of intracellular Ca(2+)-dependent proteolysis.
14612448 2004 Calpain-1 regulates Bax and subsequent Smac-dependent caspase-3 activation in neutrophil apoptosis.
14559243 2003 Association of the calpain/calpastatin network with subcellular organelles.
12923177 2003 Interaction of the ERC family of RIM-binding proteins with the liprin-alpha family of multidomain proteins.
12684003 2003 A structural model for the inhibition of calpain by calpastatin: crystal structures of the native domain VI of calpain and its complexes with calpastatin peptide and a small molecule inhibitor.
12591934 2003 Subcellular localization and in vivo subunit interactions of ubiquitous mu-calpain.
12482888 2002 Expression of a calpastatin transgene slows muscle wasting and obviates changes in myosin isoform expression during murine muscle disuse.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12354790 2002 Overexpression of a calpastatin transgene in mdx muscle reduces dystrophic pathology.
11978196 2002 Cloning and characterization of a novel isoform of calpastatin in human adult testis.
11849768 2002 Mutation analysis of the calpastatin gene (CAST) in patients with Alzheimer's disease.
11230166 2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.
11076863 2000 DNA cloning using in vitro site-specific recombination.
10942721 2000 Impairment of NF-kappaB activation and modulation of gene expression by calpastatin.
10859257 2000 Molecular cloning and characterization of functional domains of a human testis-specific isoform of calpastatin.
10822276 2000 Increase in ultraviolet sensitivity by overexpression of calpastatin in ultraviolet-resistant UVr-1 cells derived from ultraviolet-sensitive human RSa cells.
10731697 2000 Caspases cleave the amino-terminal calpain inhibitory unit of calpastatin during apoptosis in human Jurkat T cells.
10600505 1999 Inflammatory cytokines induced down-regulation of m-calpain mRNA expression in fibroblastic synoviocytes from patients with osteoarthritis and rheumatoid arthritis.
9873017 1999 Tumor necrosis factor-alpha-inducible IkappaBalpha proteolysis mediated by cytosolic m-calpain. A mechanism parallel to the ubiquitin-proteasome pathway for nuclear factor-kappab activation.
9705209 1998 Caspase-mediated fragmentation of calpain inhibitor protein calpastatin during apoptosis.
9213221 1997 Identification of mu-, m-calpains and calpastatin and capture of mu-calpain activation in endothelial cells.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
8340353 1993 Requirement of different subdomains of calpastatin for calpain inhibition and for binding to calmodulin-like domains.
7998969 1994 Calpastatin in erythrocytes of young and old individuals.
7951045 1994 Calpastatin gene in human testis.
7710300 Expression of the calpastatin gene segment during spermiogenesis in human testis: an in situ hybridization study.
7706496 1995 Detection and expression of a cDNA clone that encodes a polypeptide containing two inhibitory domains of human calpastatin and its recognition by rheumatoid arthritis sera.
7638179 1995 Autoantibodies to calpastatin (an endogenous inhibitor for calcium-dependent neutral protease, calpain) in systemic rheumatic diseases.
2849943 1988 Characterization of the calpastatin defect in erythrocytes from patients with essential hypertension.
2577276 1989 cDNA cloning of human calpastatin: sequence homology among human, pig, and rabbit calpastatins.
2559735 1989 Cloning and expression of the genes for calpains and calpastatins.
2553724 1989 Inhibition of calpain by a synthetic oligopeptide corresponding to an exon of the human calpastatin gene.
2548504 1989 Intracellular regulatory system involving calpain and calpastatin.
2407243 1990 Characterization of a functional domain of human calpastatin.
2265559 1990 Assignment of the human calpastatin gene (CAST) to chromosome 5 at region q14----q22.
1995645 1991 Phosphorylation and subcellular distribution of calpastatin in human hematopoietic system cells.
1569094 1992 Molecular diversity in amino-terminal domains of human calpastatin by exon skipping.