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FLASH GENE

Symbol

CAV3

contributors: mct/npt - updated : 17-03-2017

HGNC name	caveolin 3
HGNC id	1529

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	LGMD1C limb-girdle muscular dystrophy 1C LQT9 long QT syndrome 9 RMD2 rippling muscle disease 2
Location	3p25.3      Physical location : 8.775.485 - 8.788.450
Synonym name	M-caveolin
Synonym symbol(s)	VIP21, MGC126100, MGC126101, MGC126129, VIP-21

DNA

TYPE	functioning gene
STRUCTURE	12.96 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001234 3 splicing 1329 NP_001225 23 151 - 1996 8567687 NM_033337 2 splicing 1425 NP_203123 17.3 151 - 1996 8567687

EXPRESSION

Type	restricted

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 atrium       Homo sapiens Adult   heart ventricle       Homo sapiens Adult

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Muscular myocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal (AA 1–53), containing a signature sequence (AA 41–48, FEDVIAEP) that is present in all caveolins (Gazzerro 2010)
	a WW-like domain
	a scaffolding (AA 54–73),
	a transmembrane (AA 74–106), which forms a hairpin loop in the sarcolemma, allowing both the N- and C-terminal ends to face the cytoplasm (Gazzerro 2010)
	C-terminal (AA 107–151)

conjugated

Other

mono polymer

homomer

HOMOLOGY

interspecies

ortholog to murine Cav3

Homologene

FAMILY

caveolin family

CATEGORY

structural protein

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
text	colocalizing with dystrophin in the sarcolemma
	expressed at the neuromuscular junction, and associates with the nicotinic acetylcholine receptor CHRNA4 (Hezel 2010)
	CAV3 is localized predominantly in the caveolae, small invaginations of the plasma membrane

basic FUNCTION	playing a putative role in the formation of caveolae membranes
	caveolin-3 inhibits growth signal in cardiac myoblasts in a Ca2+-dependent manner
	has a role in the regulation of energy metabolism of muscle cells (Gazzerro 2010)
	structural protein component of caveolae in muscle cells (Hezel 2010)
	critical component of the signaling machinery that drives nicotinic acetylcholine receptor clustering and controls neuromuscular junction function (Hezel 2010)
	sequester fatty acids on the cytoplasmic leaflet of the plasma membrane, augment triglyceride formation and protect cells from lipotoxicity (Simard 2009)
	negatively regulates KCNJ11/SUR2A channel function (Garg 2009)
	role for caveolin-3 in dihydropyridine receptor (QDPR) functional regulation and/or T-tubular membrane localization
	CAV3 expression and its association with ionic channels likely represent a crucial step of cardiac maturation
	in the heart CAV3 is the main component of caveolae, plasma membrane domains that regulate multiple cellular processes highly relevant for cardiac excitability, such as trafficking, calcium homeostasis, signal transduction and cellular response to injury
	CAV3 protein can modify integrin function and mechanotransduction in the cardiac myocytes (CM) and intact heart
	CAV3 may be a novel participant in B-cell expression, T-cell cytokine production and activation of inflammation
	pathological cardiac hypertrophy is characterized by subcellular remodeling of the ventricular myocyte with a reduction in the scaffolding protein CAV3
	stable CAV3 expression is essential for protecting the signaling mechanisms in pharmacologically and pressure overload-induced cardiac hypertrophy

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

text	muscle development

PATHWAY

metabolism

signaling

a component	component of dystrophin complex
	CAV3, NEDD4L, and KCNH2 likely form a complex in the plasma membrane

INTERACTION

DNA

RNA

small molecule

protein	DYSF (functional role for caveolins in a novel post-Golgi trafficking pathway followed by dysferlin)
	interaction between VDR and CAV3 (providing that VDR plays a role in regulation of heart structure and function) (Zhao (2010)
	neuronal nitric oxide synthase (NOS1) in skeletal muscle fibers, maintaining the enzyme in an inactive conformation
	dystrophin-glycoprotein complex
	beta dystroglycan to regulate the recruitment of dystrophin to the sarcolemma
	direct molecular interaction between CAV3 and QDPR which is likely to underlie their functional link and whose loss might therefore be involved in pathophysiological mechanisms associated to muscle caveolinopathies
	CAV3 enhances ubiquitin ligase NEDD4L interaction with mature KCNH2 channels in the plasma membrane, leading to decreased channel expression
	building block of caveolae as well as a regulator of a number of physiological processes by facilitating the formation of multiprotein signaling complexes
	developmental change in HCN4-CAV3 association in human embryonic stem cell-derived cardiomyocytes (hESC-CM)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

LGMD1C , RMD2 , LQT9

related resource

Limb-Girdle Muscular dystrophy type 1C

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   with presenilin in astrocytes of Alzheimer disease and leading to alteration of APP processing constitutional     --over   in skeletal muscle fibers inducing a muscular dystrophy Duchenne-like constitutional     --over   in idiopathic hyper-CK-emia constitutional       loss of function palmitate-induced loss of CAV3 results in cardiac contractile dysfunction via a defect in calcium-induced calcium release

Susceptibility

to cardiac death

Variant & Polymorphism other	CAV3 V82I variant on cell viability may participate in determining the susceptibility to cardiac death

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	caveolin-3 null mice show abnormal neuromuscular junction activity that is consistent with altered CHRNA4 localization at the sarcolemma (Hezel 2010)
	caveolin-3 knockout (Cav-3KO) mice exhibited modestly increased myocardial ischemia/reperfusion injury (increased infarct size, apoptosis, and poorer cardiac function recovery