CAST

Protein identityUniProt · HPA

UniProt accession

P20810

Gene

CAST

Ensembl

ENSG00000153113

Chromosome

5

Canonical length

708 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Endoplasmic reticulum,Plasma membrane,Cytosol

OverviewNCBI Gene

The protein encoded by this gene is an endogenous calpain (calcium-dependent cysteine protease) inhibitor. It consists of an N-terminal domain L and four repetitive calpain-inhibition domains (domains 1-4), and it is involved in the proteolysis of amyloid precursor protein. The calpain/calpastatin system is involved in numerous membrane fusion events, such as neural vesicle exocytosis and platelet and red-cell aggregation. The encoded protein is also thought to affect the expression levels of genes encoding structural or regulatory proteins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2010]

Canonical amino-acid sequenceUniProt

708 residues, UniProt reviewed canonical sequence.

>P20810|CAST
     1  MNPTETKAIP VSQQMEGPHL PNKKKHKKQA VKTEPEKKSQ STKLSVVHEK KSQEGKPKEH
    61  TEPKSLPKQA SDTGSNDAHN KKAVSRSAEQ QPSEKSTEPK TKPQDMISAG GESVAGITAI
   121  SGKPGDKKKE KKSLTPAVPV ESKPDKPSGK SGMDAALDDL IDTLGGPEET EEENTTYTGP
   181  EVSDPMSSTY IEELGKREVT IPPKYRELLA KKEGITGPPA DSSKPIGPDD AIDALSSDFT
   241  CGSPTAAGKK TEKEESTEVL KAQSAGTVRS AAPPQEKKRK VEKDTMSDQA LEALSASLGT
   301  RQAEPELDLR SIKEVDEAKA KEEKLEKCGE DDETIPSEYR LKPATDKDGK PLLPEPEEKP
   361  KPRSESELID ELSEDFDRSE CKEKPSKPTE KTEESKAAAP APVSEAVCRT SMCSIQSAPP
   421  EPATLKGTVP DDAVEALADS LGKKEADPED GKPVMDKVKE KAKEEDREKL GEKEETIPPD
   481  YRLEEVKDKD GKPLLPKESK EQLPPMSEDF LLDALSEDFS GPQNASSLKF EDAKLAAAIS
   541  EVVSQTPAST TQAGAPPRDT SQSDKDLDDA LDKLSDSLGQ RQPDPDENKP MEDKVKEKAK
   601  AEHRDKLGER DDTIPPEYRH LLDDNGQDKP VKPPTKKSED SKKPADDQDP IDALSGDLDS
   661  CPSTTETSQN TAKDKCKKAA SSSKAPKNGG KAKDSAKTTE ETSKPKDD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CAST can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.66

Highest tissue expression

322 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CAST.

Disease | AllUniProt

Conditions CAST is implicated in, by any mechanism.

• Peeling skin with leukonychia, acral punctate keratoses, cheilitis, and knuckle pads (PLACK) MIM:616295

Disease | GeneticClinVar

14 pathogenic / likely-pathogenic of 319 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome
• CAST-related disorder

Disease | ImmuneIEDB

Conditions an epitope on CAST was assayed in.

• rheumatoid arthritis B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against CAST are reported. Each links to that disease's full target list.

• Arthritis, Rheumatoid 15

ReferencesPubMed · IEDB

Publications for CAST from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.78

gnomAD pLI

0

gnomAD missense Z

-0.38

DepMap mean gene effect

-0.28

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• negative regulation of type B pancreatic cell apoptotic process
• presynaptic active zone organization

Molecular functions

• cadherin binding
• endopeptidase inhibitor activity
• RNA binding
• calcium-dependent cysteine-type endopeptidase inhibitor activity

Cellular components

• cytoplasm
• cytosol
• endoplasmic reticulum
• membrane

Protein domainsUniProt · Pfam · InterPro

• Proteinase inhibitor I27, calpastatin
• Calpastatin
• Calpain inhibitor

KeywordsUniProt

• Acetylation
• Isopeptide bond
• Palmoplantar keratoderma
• Phosphoprotein
• Protease inhibitor
• Repeat
• Thiol protease inhibitor
• Ubl conjugation