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FLASH GENE

Symbol

CAPN1

contributors: mct/pgu - updated : 06-06-2016

HGNC name	calpain 1, (mu/I) large subunit
HGNC id	1476

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001198868 22 - 3125 NP_001185797 - 714 - 2016 27153400 NM_001198869 22 - 3094 NP_001185798 - 714 - 2016 27153400 NM_005186 22 - 3110 NP_005177 - 714 - 2016 27153400

EXPRESSION

Type	ubiquitous

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 Digestive intestine large intestine colon   moderately   mouth       predominantly Lymphoid/Immune spleen       moderately   thymus       highly   tonsils       highly Nervous brain       highly Homo sapiens Respiratory respiratory tract larynx     highly Urinary bladder       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central     highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic platelet Homo sapiens Adult

cell lineage
cell lines
fluid/secretion	blood, lymph

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal regulatory domain processed after activation (I), an amphipathic -helical domain and a mitochondrial targeting sequence
	a cysteine protease domain (II)
	a linker domain (III)
	a calcium binding domain
	five calmodulin-like EF hand motifs (IV)

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	homolog to rattus Capn1 (89.34 pc)
	homolog to murine Capn1 (89.34 pc)

Homologene

FAMILY

peptidase C2 family, papain superfamily

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,lysosome
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,chromatin/chromosome
text	translocated to the plasma membrane upon Ca2+ binding
	imported into mitochondria
	normally localizes to the interphase nuclei and chromatin

basic FUNCTION	calcium dependent neutral cysteine proteinase (non lysosomal) catalyzing limited proteolysis of substrates involved in cytoskeletal remodelling and signal transduction
	regulating cell migration by proteolysing filamin and talin
	involved in positive regulation of cell proliferation
	may play a role in mitochondrial apoptotic signalling
	CAPN1, and CAPN2 facilitates actin reorganization during glucose-stimulated insulin secretion
	plays an important role in controlling the levels of autophagy in normal living cells by regulating the levels of a key signaling molecule, ATG12-ATG5 conjugate
	CASP1-proteasome-dependent NFKBIA polymer degradation may contribute to cancer progression through constitutive NF-kappaB activation
	involved in physiological platelet activation, and in diabetes-associated platelet hyperactivation
	CAPN1 and CAPN2 are critical modulator for regulation of CDKN1B in cells of the osteoblast lineage
	CAPN1 and CAPN2 at least in part share similar functions under the control of calpastatin (CAST)
	intracellular, non-lysosomal cytoplasmic cysteine endopeptidase
	calcium regulated cysteine proteases that have been described in a wide range of cellular processes, including apoptosis, migration and cell cycle regulation
	role for calpain 1 in repressing differentiation, thus maintaining a proliferative neural stem cell pool
	CAPN1- regulation of MMP2 activity in vascular smooth muscle cells facilitates age-associated aortic wall calcification and fibrosis
	CAPN1 is identified as a novel regulator in IgE-mediated mast cell activation 7)
	critical role of CAPN1 in the early phase and during progression of amyotrophic lateral sclerosis (ALS)
	CAPN1 induces ER stress and MAPK8/MAPK9 activation, thereby mediating apoptosis in cardiomyocytes
	its activation plays critical role in vascular calcification caused by oxLDL, which might be mediated by inorganic pyrophosphate (PPi)metabolism disorder
	is involved in synaptic plasticity, synaptic restructuring, and axon maturation and maintenance

CELLULAR PROCESS	cell life, proliferation/growth
	cell organization/biogenesis
	cell migration & motility

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

heterodimerizing with the small subunit CAPNS1

INTERACTION

DNA

RNA

small molecule	metal binding,
	calcium Ca2+

protein	CAPN1-activated form of CASP7 has unique enzymatic activity, localization, and binding affinity when compared with the caspase-activated form
	is essential for the proteolytic processing of FLG2 and the deimination accelerates this process
	RAD21 cleavage by CAPN1 promotes separation of chromosome arms, which coincides with a calcium-induced partial loss of cohesin at several chromosomal loci
	is a RAD21 peptidase (cleaves RAD21 at L192, in a calcium-dependent manner)
	CAPN1 and CAPN2 cleave and functionally activate TRPC5
	phosphorylation of ZFHX3 was an important regulatory mechanism protecting it from digestion by CAPN1
	ATXN3 is a substrate of CAPN1 and CAPN2 and these proteases present promising targets for therapeutic intervention
	overactivation of CAPN1 caused by calcium overload proteolyses CREB1, resulting in a reduction of SLC2A3 expression and consequently impairing glucose uptake and metabolism in AD brain
	CAST inhibit CAPN1 activity and thus prevent cell death
	dual role for CAPN1 in the weaned gland after the pregnancy/lactation cycle, controlling programmed cell death and participating in the epigenetic programme during adipocyte differentiation
	interacts with CDK5 and NR2B to control NMDA-receptor degradation and synaptic plasticity
	OLR1 is, at least in part, responsible for the inhibitory effect of oxidized low-density lipoprotein (ox-LDL) on macrophage migration and this process involves CAPN1 and CAPN2

cell & other

REGULATION

activated by

micromolar concentrations of calcium

inhibited by

calpastatin CAST

ASSOCIATED DISORDERS

corresponding disease(s)

SPG76

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in higher grading of the ovarian carcinoma constitutional     --over   associated with an increase in mitochondrial ROS generation and oxidative damage and a reduction in ATP synthase alpha(ATP5A1) protein and ATP synthase activity

Susceptibility

Variant & Polymorphism

Candidate gene	is a novel molecular candidate to retard age-associated extracellular matrix remodeling and its attendant risk for hypertension and atherosclerosis
Marker
Therapy target
	System Type Disorder Pubmed allergy     potential therapeutic target for the management of allergic inflammation

ANIMAL & CELL MODELS

	Capn1 knock-out mice may serve as a useful model system for neuronal protection and apoptosis in traumatic brain injury and other neurodegenerative disorders in which oxidative stress plays a role
	Calpain-1 protein and activity in mitochondria were elevated in diabetic mouse hearts