Cast calpastatin [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Castprovided by RGD
Official Full Name: calpastatinprovided by RGD
Primary source: RGD:2278
See related: EnsemblRapid:ENSRNOG00000010286 AllianceGenome:RGD:2278
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: Enables calcium-dependent cysteine-type endopeptidase inhibitor activity and protease binding activity. Involved in several processes, including animal organ regeneration; myoblast fusion; and skeletal muscle atrophy. Located in membrane and postsynaptic density. Used to study brain ischemia. Biomarker of alcohol use disorder; hypertension; and muscular atrophy. Human ortholog(s) of this gene implicated in PLACK syndrome; Parkinson's disease; autoimmune disease (multiple); congenital myasthenic syndrome 1A; and vasculitis. Orthologous to human CAST (calpastatin). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in Lung (RPKM 280.0), Spleen (RPKM 229.5) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 2q11

Exon count:: 31

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	2	NC_086020.1 (5707633..5817213, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	2	NC_051337.1 (3973112..4082658, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	2	NC_005101.4 (1452111..1561669, complement)

Chromosome 2 - NC_086020.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

calpastatin protein and mRNA levels were low at early developmental time points and increased dramatically by postnatal day 30
Title: Calpain 1 and Calpastatin expression is developmentally regulated in rat brain.
Over-expression of calpastatin inhibits calpain activation and improves myocardial function in endotoxaemia.
Title: Over-expression of calpastatin inhibits calpain activation and attenuates myocardial dysfunction during endotoxaemia.
In hippocampal slices, both basic excitability and long-term synaptic efficacy are significantly increased upon treatment with a synthetic membrane-permeable activator calpastatin peptide.
Title: Synthetic calpain activator boosts neuronal excitability without extra Ca2+.
2.4-A-resolution crystal structure of the calcium-bound calpain 2 heterodimer bound by one of the four inhibitory domains of calpastatin
Title: Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin.
3.0 A structure of Ca(2+)-bound m-calpain in complex with the first calpastatin repeat, both from rat, revealing the mechanism of exclusive specificity
Title: Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains.
Role of the calpain-calpastatin system in the density-dependent growth arrest.
Title: Role of the calpain-calpastatin system in the density-dependent growth arrest.
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
Title: Regulation of calpain activity by c-Myc through calpastatin and promotion of transformation in c-Myc-negative cells by calpastatin suppression.
Neuroprotective mechanism of taurine due to up-regulating calpastatin and down-regulating calpain and caspase-3 during focal cerebral ischemia.
Title: Neuroprotective mechanism of taurine due to up-regulating calpastatin and down-regulating calpain and caspase-3 during focal cerebral ischemia.
It was concluded that the presence of the XL-domain in these isoforms is not relevant for the formation of the calpain/calpastatin complex in the absence of calcium, that is the interaction of calpastatin with inactive calpain.
Title: Multiple rat brain calpastatin forms are produced by distinct starting points and alternative splicing of the N-terminal exons.
Although desmin depletion was not statistical significance, a significant inverse relationship was found between the mu-calpain/calpastatin ratio and the amount of desmin in myofibrils during hindlimb unweighting and reweighting in skeletal muscle.
Title: Calpain/calpastatin activities and substrate depletion patterns during hindlimb unweighting and reweighting in skeletal muscle.

Submit: New GeneRIF Correction See all GeneRIFs (18)

General gene information

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Markers

AU025058 (e-PCR)
- UniSTS:115637

AU049142 (e-PCR)
- UniSTS:145590

RH138573 (e-PCR)
- UniSTS:220660

RH127627 (e-PCR)
- UniSTS:210937

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables calcium-dependent cysteine-type endopeptidase inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium-dependent cysteine-type endopeptidase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables calcium-dependent cysteine-type endopeptidase inhibitor activity	IEA Inferred from Electronic Annotation more info
enables calcium-dependent cysteine-type endopeptidase inhibitor activity	ISO Inferred from Sequence Orthology more info
enables cysteine-type endopeptidase inhibitor activity	IEA Inferred from Electronic Annotation more info
enables protease binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in animal organ regeneration	IEP Inferred from Expression Pattern more info	PubMed
involved_in egg activation	IDA Inferred from Direct Assay more info	PubMed
involved_in inhibition of cysteine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info
involved_in liver development	IEP Inferred from Expression Pattern more info	PubMed
involved_in myoblast differentiation	IEP Inferred from Expression Pattern more info	PubMed
involved_in myoblast fusion	IEP Inferred from Expression Pattern more info	PubMed
involved_in negative regulation of catalytic activity	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of peptidase activity	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of type B pancreatic cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of type B pancreatic cell apoptotic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein catabolic process	TAS Traceable Author Statement more info	PubMed
involved_in skeletal muscle atrophy	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in membrane	ISO Inferred from Sequence Orthology more info
located_in postsynaptic density	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: calpastatin

Names: calpain inhibitor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001033715.1 → NP_001028887.1 calpastatin isoform b

See identical proteins and their annotated locations for NP_001028887.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.

Source sequence(s)

BC091239

UniProtKB/Swiss-Prot

A5GXY4, A5GXY5, A5GXY6, A5GXY7, A5GXY8, A5GXY9, A5GXZ7, O55151, O55152, O55153, P27321, Q5BK19, Q99MG1, Q99MG2

UniProtKB/TrEMBL

A0A0G2JSY2

Conserved Domains (1) summary

pfam00748
Location:233 → 357

Calpain_inhib; Calpain inhibitor
NM_001033716.1 → NP_001028888.1 calpastatin isoform c

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks two in-frame exons compared to variant 1. The resulting isoform (c) has the same N- and C-termini but is shorter compared to isoform a.

Source sequence(s)

AF346597, BC091239, Y13589

UniProtKB/Swiss-Prot

A5GXY4, A5GXY5, A5GXY6, A5GXY7, A5GXY8, A5GXY9, A5GXZ7, O55151, O55152, O55153, P27321, Q5BK19, Q99MG1, Q99MG2

UniProtKB/TrEMBL

D3ZL24

Related

ENSRNOP00000058756.3, ENSRNOT00000062052.6

Conserved Domains (1) summary

pfam00748
Location:210 → 334

Calpain_inhib; Calpain inhibitor
NM_053295.2 → NP_445747.2 calpastatin isoform a

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).

Source sequence(s)

BC091239, Y13588

UniProtKB/Swiss-Prot

A5GXY4, A5GXY5, A5GXY6, A5GXY7, A5GXY8, A5GXY9, A5GXZ7, O55151, O55152, O55153, P27321, Q5BK19, Q99MG1, Q99MG2

Related

ENSRNOP00000058759.3, ENSRNOT00000062055.7

Conserved Domains (1) summary

pfam00748
Location:271 → 395

Calpain_inhib; Calpain inhibitor