CAPN10

Protein identityUniProt · HPA

UniProt accession

Q9HC96

Gene

CAPN10

Ensembl

ENSG00000142330

Chromosome

2

Canonical length

672 aa

Protein class

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

Subcellular location

Mitochondria,Cytosol

OverviewNCBI Gene

Calpains represent a ubiquitous, well-conserved family of calcium-dependent cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large catalytic subunit has four domains: domain I, the N-terminal regulatory domain that is processed upon calpain activation; domain II, the protease domain; domain III, a linker domain of unknown function; and domain IV, the calmodulin-like calcium-binding domain. This gene encodes a large subunit. It is an atypical calpain in that it lacks the calmodulin-like calcium-binding domain and instead has a divergent C-terminal domain. It is similar in organization to calpains 5 and 6. This gene is associated with type 2 or non-insulin-dependent diabetes mellitus (NIDDM), and is located within the NIDDM1 region. Multiple alternative transcript variants have been described for this gene. [provided by RefSeq, Sep 2010]

Canonical amino-acid sequenceUniProt

672 residues, UniProt reviewed canonical sequence.

>Q9HC96|CAPN10
     1  MRAGRGATPA RELFRDAAFP AADSSLFCDL STPLAQFRED ITWRRPQEIC ATPRLFPDDP
    61  REGQVKQGLL GDCWFLCACA ALQKSRHLLD QVIPPGQPSW ADQEYRGSFT CRIWQFGRWV
   121  EVTTDDRLPC LAGRLCFSRC QREDVFWLPL LEKVYAKVHG SYEHLWAGQV ADALVDLTGG
   181  LAERWNLKGV AGSGGQQDRP GRWEHRTCRQ LLHLKDQCLI SCCVLSPRAG ARELGEFHAF
   241  IVSDLRELQG QAGQCILLLR IQNPWGRRCW QGLWREGGEG WSQVDAAVAS ELLSQLQEGE
   301  FWVEEEEFLR EFDELTVGYP VTEAGHLQSL YTERLLCHTR ALPGAWVKGQ SAGGCRNNSG
   361  FPSNPKFWLR VSEPSEVYIA VLQRSRLHAA DWAGRARALV GDSHTSWSPA SIPGKHYQAV
   421  GLHLWKVEKR RVNLPRVLSM PPVAGTACHA YDREVHLRCE LSPGYYLAVP STFLKDAPGE
   481  FLLRVFSTGR VSLSAIRAVA KNTTPGAALP AGEWGTVQLR GSWRVGQTAG GSRNFASYPT
   541  NPCFPFSVPE GPGPRCVRIT LHQHCRPSDT EFHPIGFHIF QVPEGGRSQD APPLLLQEPL
   601  LSCVPHRYAQ EVSRLCLLPA GTYKVVPSTY LPDTEGAFTV TIATRIDRPS IHSQEMLGQF
   661  LQEVSIMAVM KT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CAPN10 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)

0.29

Highest tissue expression

29 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CAPN10.

Disease | AllUniProt

Conditions CAPN10 is implicated in, by any mechanism.

• Type 2 diabetes mellitus 1 (T2D1) MIM:601283

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 197 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Inborn genetic diseases
• CAPN10-related disorder
• Diabetes mellitus, noninsulin-dependent, 1

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)

1

gnomAD pLI

0

gnomAD missense Z

1.17

DepMap mean gene effect

-0.01

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

• cellular component disassembly involved in execution phase of apoptosis
• cellular response to insulin stimulus
• positive regulation of D-glucose import
• positive regulation of insulin secretion
• positive regulation of type B pancreatic cell apoptotic process
• proteolysis
• regulation of actin cytoskeleton organization
• type B pancreatic cell apoptotic process
• vesicle-mediated transport to the plasma membrane

Molecular functions

• calcium-dependent cysteine-type endopeptidase activity
• cytoskeletal protein binding
• SNARE binding

Cellular components

• cytoplasm
• cytosol
• mitochondrion
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Cysteine peptidase, cysteine active site
• Peptidase C2, calpain, catalytic domain
• 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

KeywordsUniProt

• Diabetes mellitus
• Hydrolase
• Protease
• Repeat
• Thiol protease