Human Gene CAV3 (uc003brb.3) Description and Page Index
  Description: Homo sapiens caveolin 3 (CAV3), transcript variant 1, mRNA.
RefSeq Summary (NM_033337): This gene encodes a caveolin family member, which functions as a component of the caveolae plasma membranes found in most cell types. Caveolin proteins are proposed to be scaffolding proteins for organizing and concentrating certain caveolin-interacting molecules. Mutations identified in this gene lead to interference with protein oligomerization or intra-cellular routing, disrupting caveolae formation and resulting in Limb-Girdle muscular dystrophy type-1C (LGMD-1C), hyperCKemia or rippling muscle disease (RMD). Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr3:8,775,486-8,788,451 Size: 12,966 Total Exon Count: 2 Strand: +
Coding Region
   Position: hg19 chr3:8,775,563-8,787,553 Size: 11,991 Coding Exon Count: 2 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:8,775,486-8,788,451)mRNA (may differ from genome)Protein (151 aa)
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OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: CAV3_HUMAN
DESCRIPTION: RecName: Full=Caveolin-3; AltName: Full=M-caveolin;
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. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress.
SUBUNIT: Homooligomer. Interacts with DLG1 and KCNA5; forms a ternary complex (By similarity). Interacts with TRIM72 (By similarity). Interacts with MUSK; may regulate MUSK signaling (By similarity). Interacts with DAG1 (via its C-terminal); the interaction prevents binding of DAG1 with DMD. Interacts with DYSF.
SUBCELLULAR LOCATION: Golgi apparatus membrane; Peripheral membrane protein (By similarity). Cell membrane; Peripheral membrane protein (By similarity). Membrane, caveola; Peripheral membrane protein (By similarity). Note=Potential hairpin-like structure in the membrane. Membrane protein of caveolae (By similarity).
TISSUE SPECIFICITY: Expressed predominantly in muscle.
PTM: Sumoylation with SUMO3 by PIAS4 may reduce agonist-induced internalization and desensitization of adrenergic receptor ABRD2.
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.
DISEASE: Defects in CAV3 are a cause of hyperCKmia (HYPCK) [MIM:123320]. It is a disease characterized by persistent elevated levels of serum creatine kinase without muscle weakness.
DISEASE: Defects in CAV3 are a cause of rippling muscle disease (RMD) [MIM:606072]. RMD is a rare 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.
DISEASE: Defects in CAV3 are a cause of familial hypertrophic cardiomyopathy (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.
DISEASE: 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.
DISEASE: 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.
DISEASE: Defects in CAV3 are the cause of myopathy distal Tateyama type (MPDT) [MIM:614321]. A disorder characterized by progressive muscular atrophy and muscle weakness beginning in the hands, the legs, or the feet. Muscle atrophy may be restricted to the small muscles of the hands and feet.
SIMILARITY: Belongs to the caveolin family.
CAUTION: It is uncertain whether Met-1 or Met-2 is the initiator.
SEQUENCE CAUTION: Sequence=AAC14931.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=BAF84581.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
WEB RESOURCE: Name=CAV3/LGMD1C; Note=Caveolin-3/LGMD-1C page; URL="http://www.dmd.nl/cav3_home.html";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CAV3";
WEB RESOURCE: Name=Wikipedia; Note=Caveolin entry; URL="http://en.wikipedia.org/wiki/Caveolin";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): CAV3
CDC HuGE Published Literature: CAV3

-  MalaCards Disease Associations
  MalaCards Gene Search: CAV3
Diseases sorted by gene-association score: rippling muscle disease* (1624), muscular dystrophy, limb-girdle, type ic* (1581), long qt syndrome 9* (1347), myopathy, distal, tateyama type* (1230), creatine phosphokinase, elevated serum* (1219), cardiomyopathy, familial hypertrophic* (475), cav3-related distal myopathy* (400), isolated asymptomatic elevation of creatine phosphokinase* (350), isolated hyperckemia* (231), long qt syndrome* (223), caveolinopathies* (219), sudden infant death syndrome* (147), cav3-related sudden infant death syndrome* (100), long qt syndrome 1* (97), limb-girdle muscular dystrophy (34), muscular dystrophy, limb-girdle, type 1b (18), muscular dystrophy (17), autosomal dominant limb-girdle muscular dystrophy (16), distal muscular dystrophy (13), autosomal recessive limb-girdle muscular dystrophy type 2b (12), muscular dystrophy, limb-girdle, type 1a (10), duchenne muscular dystrophy (9), 3p- syndrome (8), progressive muscular atrophy (8), myopathy (8), muscular dystrophy, limb-girdle, type 2a (7), muscular dystrophy, limb-girdle, type 1f (7), syncope (6), muscular dystrophy, limb-girdle, type 1e (6), muscle disorders (6), jervell and lange-nielsen syndrome (6), muscular atrophy (5), cardiomyopathy (5), muscular dystrophy-dystroglycanopathy , type b, 5 (4), brugada syndrome (2), muscle tissue disease (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 22.15 RPKM in Muscle - Skeletal
Total median expression: 43.00 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -15.3077-0.199 Picture PostScript Text
3' UTR -343.81898-0.383 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001612 - Caveolin
IPR018361 - Caveolin_CS

Pfam Domains:
PF01146 - Caveolin

ModBase Predicted Comparative 3D Structure on P56539
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005246 calcium channel regulator activity
GO:0005515 protein binding
GO:0008022 protein C-terminus binding
GO:0017080 sodium channel regulator activity
GO:0019870 potassium channel inhibitor activity
GO:0019899 enzyme binding
GO:0032947 protein complex scaffold
GO:0043014 alpha-tubulin binding
GO:0044325 ion channel binding
GO:0044877 macromolecular complex binding
GO:0050998 nitric-oxide synthase binding
GO:0071253 connexin binding

Biological Process:
GO:0001778 plasma membrane repair
GO:0002027 regulation of heart rate
GO:0006469 negative regulation of protein kinase activity
GO:0006641 triglyceride metabolic process
GO:0006897 endocytosis
GO:0006936 muscle contraction
GO:0007009 plasma membrane organization
GO:0007015 actin filament organization
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0007517 muscle organ development
GO:0007520 myoblast fusion
GO:0008016 regulation of heart contraction
GO:0008104 protein localization
GO:0008284 positive regulation of cell proliferation
GO:0010614 negative regulation of cardiac muscle hypertrophy
GO:0010831 positive regulation of myotube differentiation
GO:0014819 regulation of skeletal muscle contraction
GO:0014902 myotube differentiation
GO:0017015 regulation of transforming growth factor beta receptor signaling pathway
GO:0023051 regulation of signaling
GO:0030154 cell differentiation
GO:0031116 positive regulation of microtubule polymerization
GO:0031122 cytoplasmic microtubule organization
GO:0031579 membrane raft organization
GO:0033292 T-tubule organization
GO:0035995 detection of muscle stretch
GO:0038009 regulation of signal transduction by receptor internalization
GO:0042391 regulation of membrane potential
GO:0042593 glucose homeostasis
GO:0042632 cholesterol homeostasis
GO:0043407 negative regulation of MAP kinase activity
GO:0043409 negative regulation of MAPK cascade
GO:0045792 negative regulation of cell size
GO:0046716 muscle cell cellular homeostasis
GO:0051001 negative regulation of nitric-oxide synthase activity
GO:0051394 regulation of nerve growth factor receptor activity
GO:0051647 nucleus localization
GO:0051896 regulation of protein kinase B signaling
GO:0051924 regulation of calcium ion transport
GO:0051926 negative regulation of calcium ion transport
GO:0055013 cardiac muscle cell development
GO:0055117 regulation of cardiac muscle contraction
GO:0060299 negative regulation of sarcomere organization
GO:0060307 regulation of ventricular cardiac muscle cell membrane repolarization
GO:0060347 heart trabecula formation
GO:0060373 regulation of ventricular cardiac muscle cell membrane depolarization
GO:0060762 regulation of branching involved in mammary gland duct morphogenesis
GO:0061052 negative regulation of cell growth involved in cardiac muscle cell development
GO:0070836 caveola assembly
GO:0071417 cellular response to organonitrogen compound
GO:0072659 protein localization to plasma membrane
GO:0086005 ventricular cardiac muscle cell action potential
GO:0090279 regulation of calcium ion import
GO:0098909 regulation of cardiac muscle cell action potential involved in regulation of contraction
GO:1900744 regulation of p38MAPK cascade
GO:1900825 regulation of membrane depolarization during cardiac muscle cell action potential
GO:1900826 negative regulation of membrane depolarization during cardiac muscle cell action potential
GO:1901017 negative regulation of potassium ion transmembrane transporter activity
GO:1901019 regulation of calcium ion transmembrane transporter activity
GO:1901380 negative regulation of potassium ion transmembrane transport
GO:2000009 negative regulation of protein localization to cell surface
GO:2000060 positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2000649 regulation of sodium ion transmembrane transporter activity
GO:2001288 positive regulation of caveolin-mediated endocytosis

Cellular Component:
GO:0000139 Golgi membrane
GO:0005737 cytoplasm
GO:0005783 endoplasmic reticulum
GO:0005794 Golgi apparatus
GO:0005886 plasma membrane
GO:0005901 caveola
GO:0009986 cell surface
GO:0014704 intercalated disc
GO:0016010 dystrophin-associated glycoprotein complex
GO:0016020 membrane
GO:0030018 Z disc
GO:0030315 T-tubule
GO:0031594 neuromuscular junction
GO:0031982 vesicle
GO:0032991 macromolecular complex
GO:0042383 sarcolemma
GO:0043231 intracellular membrane-bounded organelle
GO:0045121 membrane raft


-  Descriptions from all associated GenBank mRNAs
  AK291892 - Homo sapiens cDNA FLJ76415 complete cds, highly similar to Homo sapiens caveolin-3 mRNA.
BC069368 - Homo sapiens caveolin 3, mRNA (cDNA clone MGC:96959 IMAGE:7262168), complete cds.
AF036365 - Homo sapiens caveolin-3 (CAV3) mRNA, complete cds.
BC102033 - Homo sapiens caveolin 3, mRNA (cDNA clone MGC:126129 IMAGE:40033505), complete cds.
BC102036 - Homo sapiens caveolin 3, mRNA (cDNA clone MGC:126100 IMAGE:40033114), complete cds.
BC102037 - Homo sapiens caveolin 3, mRNA (cDNA clone MGC:126101 IMAGE:40033118), complete cds.
Y14747 - Homo sapiens mRNA for caveolin 3 protein.
CU686780 - Synthetic construct Homo sapiens gateway clone IMAGE:100022546 5' read CAV3 mRNA.
KJ904430 - Synthetic construct Homo sapiens clone ccsbBroadEn_13824 CAV3 gene, encodes complete protein.
KU971296 - Homo sapiens cavolin 3 mRNA, partial cds.
KJ890834 - Synthetic construct Homo sapiens clone ccsbBroadEn_00228 CAV3 gene, encodes complete protein.
KR711864 - Synthetic construct Homo sapiens clone CCSBHm_00031467 CAV3 (CAV3) mRNA, encodes complete protein.
KR711865 - Synthetic construct Homo sapiens clone CCSBHm_00031478 CAV3 (CAV3) mRNA, encodes complete protein.
KR711866 - Synthetic construct Homo sapiens clone CCSBHm_00031487 CAV3 (CAV3) mRNA, encodes complete protein.
KR711867 - Synthetic construct Homo sapiens clone CCSBHm_00031496 CAV3 (CAV3) mRNA, encodes complete protein.
AF043101 - Homo sapiens caveolin-3 mRNA, complete cds.
JD460968 - Sequence 441992 from Patent EP1572962.
JD410682 - Sequence 391706 from Patent EP1572962.
JD040078 - Sequence 21102 from Patent EP1572962.
JD290483 - Sequence 271507 from Patent EP1572962.
JD100958 - Sequence 81982 from Patent EP1572962.
JD316615 - Sequence 297639 from Patent EP1572962.
JD062376 - Sequence 43400 from Patent EP1572962.
JD475941 - Sequence 456965 from Patent EP1572962.
JD387387 - Sequence 368411 from Patent EP1572962.
JD121559 - Sequence 102583 from Patent EP1572962.
JD095311 - Sequence 76335 from Patent EP1572962.
JD147458 - Sequence 128482 from Patent EP1572962.
JD464164 - Sequence 445188 from Patent EP1572962.
JD518681 - Sequence 499705 from Patent EP1572962.
JD171922 - Sequence 152946 from Patent EP1572962.
JD337917 - Sequence 318941 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04144 - Endocytosis
hsa04510 - Focal adhesion
hsa05100 - Bacterial invasion of epithelial cells

Reactome (by CSHL, EBI, and GO)

Protein P56539 (Reactome details) participates in the following event(s):

R-HSA-5263633 DYSF, CAV3 and TRIM72 bind
R-HSA-5263628 CAV3:TRIM72:DYSF binds ANXAs
R-HSA-445355 Smooth Muscle Contraction
R-HSA-397014 Muscle contraction

-  Other Names for This Gene
  Alternate Gene Symbols: A8K777, CAV3_HUMAN, NM_033337, NP_203123, P56539, Q3T1A4
UCSC ID: uc003brb.3
RefSeq Accession: NM_033337
Protein: P56539 (aka CAV3_HUMAN)
CCDS: CCDS2569.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene CAV3:
rws (Long QT Syndrome)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_033337.2
exon count: 2CDS single in 3' UTR: no RNA size: 1435
ORF size: 456CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1112.00frame shift in genome: no % Coverage: 99.72
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: yes # AT/AC introns 0
selenocysteine: no end bleed into intron: 892# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.