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FLASH GENE

Symbol

CAPN3

contributors: mct - updated : 11-04-2014

HGNC name	calpain 3, (p94)
HGNC id	1480

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	64.22 kb     28 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000070 24 - 3316 NP_000061 94 821 - 1999 10330145 NM_024344 23 splicing 3298 NP_077320 93.3 815 - 1999 10330145 inclusion of intronic sequence between exons 16, 17 NM_173087 21 splicing 3040 NP_775110 83.5 729 lens specific 1999 10330145 alternative specific first exon, hydrolyzing substrates such as crystallins during lens cataract formation NM_173088 13 - 1661 NP_775111 - 309 - 2006 16627476 NM_173089 9 - 1291 NP_775112 - 156 - 2006 16627476 NM_173090 10 - 1309 NP_775113 - 156 - 2006 16627476 differs in the 5' UTR and uses a downstream start codon variant 8 - - 3901 isoform 8 - 426 - 2006 16627476 has an alternate 5' sequence and lacks an exon in the 3' region has a shorter and distinct N-terminus and a truncated C-terminus NM_212465 27 - 3223 NP_997630 - 728 - - variant 9 - - 3521 isoform 9 - 107 - 2006 16627476 has an alternate 5' sequence and an additional middle exon lacks a 3' exon

EXPRESSION

Rna function	mRNA is expressed at high levels in muscle and appears to have some role in developmental processes
Type	widely

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive mouth tongue     highly   pharynx       highly Hearing/Equilibrium ear inner cochlea   highly Nervous nerve cranial nerve       Reproductive female system breast mammary gland       female system uterus       Skin/Tegument skin       highly Visual eye lens     moderately Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Muscular myocyte Visual lens fibers Homo sapiens

cell lineage
cell lines
fluid/secretion	blood

at STAGE

physiological period

embryo

Text

heart

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal regulatory domain processed after activation (I)
	a cysteine protease domain (II)
	a linker domain (III)
	specific IS2 segment between domains III and IV, important functional site that may regulate the transient activation and limited proteolysis of CAPN3
	a calcium binding domain with four calmodulin-like EF hand motifs (IV)
	two nuclear localization signals (NLS)

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	ortholog to rattus capn3
	ortholog to murine Capn3

Homologene

FAMILY	papain superfamily
	calpain cysteine protease (C2) family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	localized in the N2 region of myofibrils

basic FUNCTION	calcium dependent neutral cysteine proteinase (non lysosomal)
	possessing a proteolytic activity against a potential substrate
	involved in cytoskeleton remodeling
	participating in sarcomere remodeling by acting upstream of the ubiquitin-proteasome pathway
	playing a physiological role in regulating the dysferlin protein complex
	is a critical but unstable enigmatic skeletal muscle protease
	has many attributes that make it ideally suited as a sensor of sarcomeric integrity and function, involved in its repair and maintenance
	is uniquely activated during lens fiber differentiation
	is an intracellular Na+-dependent protease, and Na+ regulate contribution of CAPN3 as a structural component in muscle cells
	is needed for the regenerative process probably during sarcomere remodeling
	having different cellular functions depending on the subcellular compartment in which it is located
	localizes to triads, where it plays an important role as a structural component and not as a protease

CELLULAR PROCESS

cell organization/biogenesis

PHYSIOLOGICAL PROCESS

development

text	cytoskeletal remodeling

PATHWAY

metabolism

signaling

signal transduction

a component

heterodimerizing with a small subunit

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	dysferlin, DYSF
	interacting with TTN
	inhibition of NACA gene expression leads to enhanced, and overexpression of NACA gene to repressed, activity of CAPN1 and, to a lesser extent, CAPN3 in myoblasts
	SIMC1 is a CAPN3-binding protein, and suppresses the protease activity of CAPN3

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

LGMD2A

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   reduced expression associated with increased in body fat, obesity and insulin resistance

Susceptibility

to idiopathic eosinophilic myositis

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	Capn3-deficient muscle in mice
	Rbfox1 downregulation and altered Capn3 splicing by Frg1 in a mouse model of Facioscapulohumeral muscular dystrophy (FSHD)