CAPN1

Protein identityUniProt · HPA

UniProt accession

P07384

Gene

CAPN1

Ensembl

ENSG00000014216

Chromosome

11

Canonical length

714 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Cytosol

OverviewNCBI Gene

The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme, calpain 1. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

Canonical amino-acid sequenceUniProt

714 residues, UniProt reviewed canonical sequence.

>P07384|CAPN1
     1  MSEEIITPVY CTGVSAQVQK QRARELGLGR HENAIKYLGQ DYEQLRVRCL QSGTLFRDEA
    61  FPPVPQSLGY KDLGPNSSKT YGIKWKRPTE LLSNPQFIVD GATRTDICQG ALGDCWLLAA
   121  IASLTLNDTL LHRVVPHGQS FQNGYAGIFH FQLWQFGEWV DVVVDDLLPI KDGKLVFVHS
   181  AEGNEFWSAL LEKAYAKVNG SYEALSGGST SEGFEDFTGG VTEWYELRKA PSDLYQIILK
   241  ALERGSLLGC SIDISSVLDM EAITFKKLVK GHAYSVTGAK QVNYRGQVVS LIRMRNPWGE
   301  VEWTGAWSDS SSEWNNVDPY ERDQLRVKME DGEFWMSFRD FMREFTRLEI CNLTPDALKS
   361  RTIRKWNTTL YEGTWRRGST AGGCRNYPAT FWVNPQFKIR LDETDDPDDY GDRESGCSFV
   421  LALMQKHRRR ERRFGRDMET IGFAVYEVPP ELVGQPAVHL KRDFFLANAS RARSEQFINL
   481  REVSTRFRLP PGEYVVVPST FEPNKEGDFV LRFFSEKSAG TVELDDQIQA NLPDEQVLSE
   541  EEIDENFKAL FRQLAGEDME ISVKELRTIL NRIISKHKDL RTKGFSLESC RSMVNLMDRD
   601  GNGKLGLVEF NILWNRIRNY LSIFRKFDLD KSGSMSAYEM RMAIESAGFK LNKKLYELII
   661  TRYSEPDLAV DFDNFVCCLV RLETMFRFFK TLDTDLDGVV TFDLFKWLQL TMFA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CAPN1 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

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

267 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CAPN1.

Disease | AllUniProt

Conditions CAPN1 is implicated in, by any mechanism.

• Spastic paraplegia 76, autosomal recessive (SPG76) MIM:616907

Disease | GeneticClinVar

50 pathogenic / likely-pathogenic of 393 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive spastic paraplegia type 76
• CAPN1-related disorder
• Hereditary spastic paraplegia 11
• Gastric cancer

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)

0.71

gnomAD pLI

0

gnomAD missense Z

1.68

DepMap mean gene effect

-0.17

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• mammary gland involution
• NMDA selective glutamate receptor signaling pathway
• positive regulation of cell population proliferation
• proteolysis
• receptor catabolic process
• regulation of catalytic activity
• regulation of macroautophagy
• self proteolysis

Molecular functions

• calcium ion binding
• calcium-dependent cysteine-type endopeptidase activity
• peptidase activity

Cellular components

• calpain complex
• cornified envelope
• cytoplasm
• cytosol
• extracellular exosome
• extracellular region
• ficolin-1-rich granule lumen
• focal adhesion
• lysosome
• membrane
• mitochondrion
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Cysteine peptidase, cysteine active site
• Peptidase C2, calpain, catalytic domain
• EF-hand domain
• EF-hand domain pair
• EF-Hand 1, calcium-binding site
• Peptidase C2, calpain, large subunit, domain III
• Peptidase C2, calpain, domain III
• Peptidase C2, calpain family
• Calpain subdomain III
• Calpain large subunit, domain III superfamily
• Papain-like cysteine peptidase superfamily
• Calpain family cysteine protease
• Calpain large subunit, domain III
• EF-hand domain pair

KeywordsUniProt

• Acetylation
• Autocatalytic cleavage
• Calcium
• Cell membrane
• Cytoplasm
• Hereditary spastic paraplegia
• Hydrolase
• Membrane
• Metal-binding
• Neurodegeneration
• Phosphoprotein
• Protease
• Repeat
• Thiol protease

InteractionsUniProt · HPA

Protein binding partners of CAPN1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CAPNS1
• MAP4
• STAT3