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Reviewed, UniProtKB/Swiss-Prot P56539 (CAV3_HUMAN)

Last modified June 16, 2009. Version 82. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Caveolin-3
Alternative name(s):
    M-caveolin
Gene names
Name: CAV3
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length151 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. May also regulate voltage-gated potassium channels.

Subunit structure

Homooligomer. Interacts with DLG1 and KCNA5; forms a ternary complex By similarity. Interacts with DYSF.

Subcellular location

Golgi apparatus membrane; Single-pass membrane protein By similarity. Cell membrane; Single-pass membrane protein By similarity. Membranecaveola; Single-pass membrane protein By similarity. Note: Potential hairpin-like structure in the membrane. Membrane protein of caveolae By similarity.

Tissue specificity

Expressed predominantly in muscle.

Involvement in disease

Defects in CAV3 are the cause of limb-girdle muscular dystrophy type 1C (LGMD1C) [MIM:607801]. LGMD1C is a myopathy characterized by calf hypertrophy and mild to moderate proximal muscle weakness. LGMD1C inheritance can be autosomal dominant or recessive. Ref.1 Ref.5 Ref.6 Ref.15 Ref.17 Ref.21 Ref.23

Defects in CAV3 are a cause of hyperCKmia [MIM:123320]. It is a disease characterized by persistent elevated levels of serum creatine kinase without muscle weakness. Ref.7 Ref.11 Ref.18 Ref.20

Defects in CAV3 are a cause of rippling muscle disease (RMD) [MIM:606072]. RMD is rare a disorder characterized by mechanically triggered contractions of skeletal muscle. In RMD, mechanical stimulation leads to electrically silent muscle contractions that spread to neighboring fibers that cause visible ripples to move over the muscle. Ref.15 Ref.9 Ref.10 Ref.16 Ref.22 Ref.24

Defects in CAV3 are a cause of cardiomyopathy familial hypertrophic (CMH) [MIM:192600]; also designated FHC or HCM. Familial hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. Ref.19

Defects in CAV3 are the cause of long QT syndrome type 9 (LQT9) [MIM:611818]. Long QT syndromes are heart disorders characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to excercise or emotional stress. They can present with a sentinel event of sudden cardiac death in infancy. Ref.25 Ref.26

Defects in CAV3 can be a cause of sudden infant death syndrome (SIDS) [MIM:272120]. SIDS is the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of clinical history. Pathophysiologic mechanisms for SIDS may include respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of metabolism, but definitive pathogenic mechanisms precipitating an infant sudden death remain elusive. Long QT syndromes-associated mutations can be responsible for some SIDS cases.

Sequence similarities

Belongs to the caveolin family.

Caution

It is uncertain whether Met-1 or Met-2 is the initiator.

Ontologies

Keywords
   Cellular componentCell membrane
Golgi apparatus
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Limb-girdle muscular dystrophy
Long QT syndrome
   DomainTransmembrane
Gene Ontology (GO)
   Biological processT-tubule organization

Traceable author statement. Source: UniProtKB

muscle organ development

Traceable author statement. Source: UniProtKB

negative regulation of MAP kinase activity

Inferred from mutant phenotype. Source: UniProtKB

negative regulation of cardiac muscle hypertrophy

Inferred from mutant phenotype. Source: UniProtKB

negative regulation of cell size

Inferred from mutant phenotype. Source: UniProtKB

negative regulation of sarcomere organization

Inferred from mutant phenotype. Source: UniProtKB

regulation of skeletal muscle contraction

Inferred from mutant phenotype. Source: UniProtKB

regulation of ventricular cardiomyocyte membrane repolarization Ref.25 Ref.26

Inferred from mutant phenotype. Source: UniProtKB

   Cellular componentGolgi membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

caveola

Inferred from electronic annotation. Source: UniProtKB-SubCell

dystrophin-associated glycoprotein complex

Inferred from direct assay. Source: UniProtKB

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular functionprotein C-terminus binding

Inferred from direct assay. Source: UniProtKB

protein complex binding

Inferred from direct assay. Source: UniProtKB

sodium channel regulator activity Ref.26

Inferred from mutant phenotype. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 151151Caveolin-3
PRO_0000144140

Regions

Topological domain1 – 8383Cytoplasmic Potential
Transmembrane84 – 10421 Potential
Topological domain105 – 15147Cytoplasmic Potential

Natural variations

Natural variant141V → L in SIDS.
VAR_043694
Natural variant271R → Q in hyperCKmia, RMD, LGMD1C and distal myopathy. Ref.17 Ref.23 Ref.7 Ref.9 Ref.10 Ref.13
VAR_011512
Natural variant281D → E in RMD and LGMD1C.
VAR_015374
Natural variant291P → L in hyperCKmia. Ref.11
VAR_029540
Natural variant331N → K in LGMD1C and distal myopathy.
VAR_021016
Natural variant441V → E in LGMD1C. Ref.21
VAR_021017
Natural variant461A → T in LGMD1C and RMD; decreased surface expression of the CAV3 protein.
VAR_011513
Natural variant461A → V in RMD. Ref.9
VAR_011514
Natural variant531S → G in RMD. Ref.24
VAR_029541
Natural variant561G → S Ref.25 Ref.3 Ref.8
VAR_029542
Natural variant571V → M in hyperCKmia. Ref.20
VAR_010742
Natural variant611S → R in a patient with mild proximal myopathy. Ref.23
VAR_026696
Natural variant64 – 663Missing in LGMD1C. Ref.5
VAR_001402
Natural variant641T → P in LGMD1C. Ref.5
VAR_021018
Natural variant641T → S in CMH. Ref.19
VAR_029543
Natural variant721C → W Ref.25 Ref.3 Ref.8
VAR_010743
Natural variant781T → M in LQT9 and SIDS.
VAR_043695
Natural variant791L → R in LQT9 and SIDS.
VAR_043696
Natural variant851A → T in LQT9. Ref.25
VAR_043697
Natural variant871L → P in RMD. dbSNP rs28936685. Ref.16
VAR_016207
Natural variant931A → T in RMD. dbSNP rs28936686. Ref.16 Ref.22
VAR_016208
Natural variant971F → C in LQT9; increase in late sodium current. Ref.25
VAR_043698
Natural variant971Missing in hyperCKmia. Ref.18 Ref.25
VAR_029544
Natural variant1051P → L in LGMD1C and RMD.
VAR_001403
Natural variant1261R → H Ref.8
VAR_029545
Natural variant1411S → R in LQT9; increase in late sodium current. Ref.25
VAR_043699

Sequences

Sequence LengthMass (Da)Tools
P56539-1 [UniParc].

Last modified July 15, 1998. Version 1.
Checksum: C695E14F5B8F4753

FASTA15117,259
        10         20         30         40         50         60 
MMAEEHTDLE AQIVKDIHCK EIDLVNRDPK NINEDIVKVD FEDVIAEPVG TYSFDGVWKV 

        70         80         90        100        110        120 
SYTTFTVSKY WCYRLLSTLL GVPLALLWGF LFACISFCHI WAVVPCIKSY LIEIQCISHI 

       130        140        150 
YSLCIRTFCN PLFAALGQVC SSIKVVLRKE V 

« Hide

References

« Hide 'large scale' references
[1]"Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy."
Minetti C., Sotgia F., Bruno C., Scartezzini P., Broda P., Bado M., Masetti E., Mazzocco M., Egeo A., Donati M.A., Volonte D., Galbiati F., Cordone G., Bricarelli F.D., Lisanti M.P., Zara F.
Nat. Genet. 18:365-368(1998) [PubMed: 9537420] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LGMD1C 64-THR--THR-66 DEL AND LEU-105.
[2]"Molecular cloning of human caveolin 3."
Biederer C., Ries S., Drobnik W., Schmitz G.
Biochim. Biophys. Acta 1406:5-9(1998) [PubMed: 9545514] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Skeletal muscle.
[3]"Caveolin-3 in muscular dystrophy."
McNally E.M., de Sa Moreira E., Duggan D.J., Bonnemann C.G., Lisanti M.P., Lidov H.G.W., Vainzof M., Passos-Bueno M.R., Hoffman E.P., Zatz M., Kunkel L.M.
Hum. Mol. Genet. 7:871-877(1998) [PubMed: 9536092] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANTS SER-56 AND TRP-72.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle."
Matsuda C., Hayashi Y.K., Ogawa M., Aoki M., Murayama K., Nishino I., Nonaka I., Arahata K., Brown R.H. Jr.
Hum. Mol. Genet. 10:1761-1766(2001) [PubMed: 11532985] [Abstract]
Cited for: INTERACTION WITH DYSF, VARIANT LGMD1C PRO-64.
[6]"Dissociation of the dystroglycan complex in caveolin-3-deficient limb girdle muscular dystrophy."
Herrmann R., Straub V., Blank M., Kutzick C., Franke N., Jacob E.N., Lenard H.-G., Kroger S., Voit T.
Hum. Mol. Genet. 9:2335-2340(2000) [PubMed: 11001938] [Abstract]
Cited for: VARIANT LGMD1C THR-46.
[7]"Mutation in the CAV3 gene causes partial caveolin-3 deficiency and hyperCKemia."
Carbone I., Bruno C., Sotgia F., Bado M., Broda P., Masetti E., Panella A., Zara F., Bricarelli F.D., Cordone G., Lisanti M.P., Minetti C.
Neurology 54:1373-1376(2000) [PubMed: 10746614] [Abstract]
Cited for: VARIANT HYPERCKMIA GLN-27.
[8]"Mutations in the caveolin-3 gene: when are they pathogenic?"
de Paula F., Vainzof M., Bernardino A.L.F., McNally E., Kunkel L.M., Zatz M.
Am. J. Med. Genet. 99:303-307(2001) [PubMed: 11251997] [Abstract]
Cited for: VARIANTS SER-56; TRP-72 AND HIS-126.
[9]"Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease."
Betz R.C., Schoser B.G.H., Kasper D., Ricker K., Ramirez A., Stein V., Torbergsen T., Lee Y.-A., Nothen M.M., Wienker T.F., Malin J.-P., Propping P., Reis A., Mortier W., Jentsch T.J., Vorgerd M., Kubisch C.
Nat. Genet. 28:218-219(2001) [PubMed: 11431690] [Abstract]
Cited for: VARIANTS RMD GLN-27; THR-46; VAL-46 AND LEU-105, SURFACE EXPRESSION OF VARIANT RMD THR-46.
[10]"A sporadic case of rippling muscle disease caused by a de novo caveolin-3 mutation."
Vorgerd M., Ricker K., Ziemssen F., Kress W., Goebel H.H., Nix W.A., Kubisch C., Schoser B.G.H., Mortier W.
Neurology 57:2273-2277(2001) [PubMed: 11756609] [Abstract]
Cited for: VARIANT RMD GLN-27.
[11]"Familial isolated hyperCKaemia associated with a new mutation in the caveolin-3 (CAV-3) gene."
Merlini L., Carbone I., Capanni C., Sabatelli P., Tortorelli S., Sotgia F., Lisanti M.P., Bruno C., Minetti C.
J. Neurol. Neurosurg. Psych. 73:65-67(2002) [PubMed: 12082049] [Abstract]
Cited for: VARIANT HYPERCKMIA LEU-29.
[12]Erratum
Merlini L., Carbone I., Capanni C., Sabatelli P., Tortorelli S., Sotgia F., Lisanti M.P., Bruno C., Minetti C.
J. Neurol. Neurosurg. Psych. 74:142-142(2003)
[13]"Mutation in the caveolin-3 gene causes a peculiar form of distal myopathy."
Tateyama M., Aoki M., Nishino I., Hayashi Y.K., Sekiguchi S., Shiga Y., Takahashi T., Onodera Y., Haginoya K., Kobayashi K., Iinuma K., Nonaka I., Arahata K., Itoyama Y.
Neurology 58:323-325(2002) [PubMed: 11805270] [Abstract]
Cited for: VARIANT DISTAL MYOPATHY GLN-27.
[14]Erratum
Tateyama M., Aoki M., Nishino I., Hayashi Y.K., Sekiguchi S., Shiga Y., Takahashi T., Onodera Y., Haginoya K., Kobayashi K., Iinuma K., Nonaka I., Arahata K., Itoyama Y.
Neurology 58:839-839(2002)
[15]"Consequences of a novel caveolin-3 mutation in a large German family."
Fischer D., Schroers A., Blumcke I., Urbach H., Zerres K., Mortier W., Vorgerd M., Schroder R.
Ann. Neurol. 53:233-241(2003) [PubMed: 12557291] [Abstract]
Cited for: VARIANT RMD GLU-28, VARIANT LGMD1C GLU-28.
[16]"Homozygous mutations in caveolin-3 cause a severe form of rippling muscle disease."
Kubisch C., Schoser B.G.H., von Duering M., Betz R.C., Goebel H.-H., Zahn S., Ehrbrecht A., Aasly J., Schroers A., Popovic N., Lochmueller H., Schroeder J.M., Bruening T., Malin J.-P., Fricke B., Meinck H.-M., Torbergsen T., Engels H., Voss B., Vorgerd M.
Ann. Neurol. 53:512-520(2003) [PubMed: 12666119] [Abstract]
Cited for: VARIANTS RMD PRO-87 AND THR-93.
[17]"Limb-girdle muscular dystrophy in a 71-year-old woman with an R27Q mutation in the CAV3 gene."
Figarella-Branger D., Pouget J., Bernard R., Krahn M., Fernandez C., Levy N., Pellissier J.F.
Neurology 61:562-564(2003) [PubMed: 12939441] [Abstract]
Cited for: VARIANT LGMD1C GLN-27.
[18]"A CAV3 microdeletion differentially affects skeletal muscle and myocardium."
Cagliani R., Bresolin N., Prelle A., Gallanti A., Fortunato F., Sironi M., Ciscato P., Fagiolari G., Bonato S., Galbiati S., Corti S., Lamperti C., Moggio M., Comi G.P.
Neurology 61:1513-1519(2003) [PubMed: 14663034] [Abstract]
Cited for: VARIANT HYPERCKMIA PHE-97 DEL.
[19]"Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy."
Hayashi T., Arimura T., Ueda K., Shibata H., Hohda S., Takahashi M., Hori H., Koga Y., Oka N., Imaizumi T., Yasunami M., Kimura A.
Biochem. Biophys. Res. Commun. 313:178-184(2004) [PubMed: 14672715] [Abstract]
Cited for: VARIANT CMH SER-64.
[20]"A novel mutation in the caveolin-3 gene causing familial isolated hyperCKaemia."
Alias L., Gallano P., Moreno D., Pujol R., Martinez-Matos J.A., Baiget M., Ferrer I., Olive M.
Neuromuscul. Disord. 14:321-324(2004) [PubMed: 15099591] [Abstract]
Cited for: VARIANT HYPERCKMIA MET-57.
[21]"Two novel CAV3 gene mutations in Japanese families."
Sugie K., Murayama K., Noguchi S., Murakami N., Mochizuki M., Hayashi Y.K., Nonaka I., Nishino I.
Neuromuscul. Disord. 14:810-814(2004) [PubMed: 15564037] [Abstract]
Cited for: VARIANTS LGMD1C LYS-33 AND GLU-44.
[22]"Autosomal recessive rippling muscle disease with homozygous CAV3 mutations."
Kubisch C., Ketelsen U.-P., Goebel I., Omran H.
Ann. Neurol. 57:303-304(2005) [PubMed: 15668980] [Abstract]
Cited for: VARIANT RMD THR-93.
[23]"Molecular and muscle pathology in a series of caveolinopathy patients."
Fulizio L., Chiara-Nascimbeni A., Fanin M., Piluso G., Politano L., Nigro V., Angelini C.
Hum. Mutat. 25:82-89(2005) [PubMed: 15580566] [Abstract]
Cited for: VARIANT HYPERCKEMIA GLN-27, VARIANT LGMD1C THR-46, VARIANTS DISTAL MYOPATHY LYS-33 AND ARG-61.
[24]"A new missense mutation in caveolin-3 gene causes rippling muscle disease."
Dotti M.T., Malandrini A., Gambelli S., Salvadori C., De Stefano N., Federico A.
J. Neurol. Sci. 243:61-64(2006) [PubMed: 16458928] [Abstract]
Cited for: VARIANT RMD GLY-53.
[25]"Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome."
Vatta M., Ackerman M.J., Ye B., Makielski J.C., Ughanze E.E., Taylor E.W., Tester D.J., Balijepalli R.C., Foell J.D., Li Z., Kamp T.J., Towbin J.A.
Circulation 114:2104-2112(2006) [PubMed: 17060380] [Abstract]
Cited for: VARIANTS LQT9 MET-78; THR-85; CYS-97 AND ARG-141, VARIANTS SER-56 AND TRP-72, CHARACTERIZATION OF VARIANTS LQT9 CYS-97 AND ARG-141.
[26]"Novel mechanism for sudden infant death syndrome: persistent late sodium current secondary to mutations in caveolin-3."
Cronk L.B., Ye B., Kaku T., Tester D.J., Vatta M., Makielski J.C., Ackerman M.J.
Heart Rhythm 4:161-166(2007) [PubMed: 17275750] [Abstract]
Cited for: VARIANTS LQT9/SIDS LEU-14; MET-78 AND ARG-79.
+Additional computationally mapped references.

Web resources

CAV3/LGMD1C

Caveolin-3/LGMD-1C page

GeneReviews
Wikipedia

Caveolin entry

Cross-references

Sequence databases

AF043101 mRNA. Translation: AAC14931.1. Different initiation.
Y14747 mRNA. Translation: CAA75042.1.
AF036367, AF036366 Genomic DNA. Translation: AAC39758.1.
AF036365 mRNA. Translation: AAC39756.1.
BC069368 mRNA. Translation: AAH69368.1.
BC102033 mRNA. Translation: AAI02034.1.
BC102036 mRNA. Translation: AAI02037.1.
BC102037 mRNA. Translation: AAI02038.1.
IPIIPI00790433.
RefSeqNP_001225.1.
NP_203123.1.
UniGeneHs.98303

3D structure databases

ModBaseSearch...

Genome annotation databases

EnsemblENSG00000182533. Homo sapiens. [Contig view]
GeneID859.
KEGGhsa:859.

Organism-specific databases

GeneCardsGC03P008750.
H-InvDBHIX0030704.
HGNCHGNC:1529. CAV3.
HPACAB017518.
CAB018557.
MIM123320. phenotype.
192600. phenotype.
272120. phenotype.
601253. gene+phenotype.
606072. phenotype.
607801. phenotype.
611818. phenotype.
Orphanet265. Autosomal dominant limb-girdle muscular dystrophy, type 1C.
155. Cardiomyopathy, hypertrophic, primary or idiopathic.
768. Long QT syndrome, familial.
PharmGKBPA26109.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP56539.
HOVERGENP56539.

Enzyme and pathway databases

Pathway_Interaction_DBpdgfrapathway. PDGFR-alpha signaling pathway.

Gene expression databases

ArrayExpressP56539.
BgeeP56539.
CleanExHS_CAV3.
GermOnlineENSG00000182533. Homo sapiens.

Family and domain databases

InterProIPR001612. Caveolin.
IPR018361. Caveolin_CS.
[Graphical view]
PANTHERPTHR10844. Caveolin. 1 hit.
PfamPF01146. Caveolin. 1 hit.
[Graphical view]
PROSITEPS01210. CAVEOLIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio3566.
SOURCESearch...

Entry information

Entry nameCAV3_HUMAN
AccessionPrimary (citable) accession number: P56539
Secondary accession number(s): Q3T1A4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1998
Last modified: June 16, 2009
This is version 82 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents