Summary: Caveolin
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Caveolin Edit Wikipedia article
| Caveolin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Caveolin | ||||||||
| Pfam | PF01146 | ||||||||
| InterPro | IPR001612 | ||||||||
| PROSITE | PDOC00930 | ||||||||
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| Caveolin 1, caveolae protein, 22kDa | |
|---|---|
| Identifiers | |
| Symbol | CAV1 |
| Alt. symbols | CAV |
| Entrez | 857 |
| HUGO | 1527 |
| OMIM | 601047 |
| RefSeq | NM_001753 |
| UniProt | Q03135 |
| Other data | |
| Locus | Chr. 7 q31 |
| Caveolin 2 | |
|---|---|
| Identifiers | |
| Symbol | CAV2 |
| Entrez | 858 |
| HUGO | 1528 |
| OMIM | 601048 |
| RefSeq | NM_001233 |
| UniProt | P51636 |
| Other data | |
| Locus | Chr. 7 q31 |
| Caveolin 3 | |
|---|---|
| Identifiers | |
| Symbol | CAV3 |
| Entrez | 859 |
| HUGO | 1529 |
| OMIM | 601253 |
| RefSeq | NM_001234 |
| UniProt | P56539 |
| Other data | |
| Locus | Chr. 3 p25 |
In molecular biology Caveolins are a family of integral membrane proteins that are the principal components of caveolae membranes and involved in receptor-independent endocytosis.[1][2][3] Caveolins may act as scaffolding proteins within caveolar membranes by compartmentalizing and concentrating signaling molecules. Various classes of signaling molecules, including G-protein subunits, receptor and non-receptor tyrosine kinases, endothelial nitric oxide synthase (eNOS), and small GTPases, bind Cav-1 through its 'caveolin-scaffolding domain'.
The caveolin gene family has three members in vertebrates: CAV1, CAV2, and CAV3, coding for the proteins caveolin-1, caveolin-2, and caveolin-3, respectively. All three members are membrane proteins with similar structure. Caveolin forms oligomers and associates with cholesterol and sphingolipids in certain areas of the cell membrane, leading to the formation of caveolae.
Contents
Structure and expression
The caveolins are similar in structure. They all form hairpin loops that are inserted into the cell membrane. Both the C-terminus and the N-terminus face the cytoplasmic side of the membrane. There are two isoforms of caveolin-1: caveolin-1α and caveolin-1β, the latter lacking a part of the N-terminus.
Caveolins are found in the majority of adherent, mammalian cells.
- Caveolin-1 is most prominently expressed in endothelial, fibrous, and adipose tissue.
- The expression pattern of caveolin-2 is similar to that of caveolin-1; it seems to be co-expressed with caveolin-1.
- The expression of caveolin-3 is restricted to striated and smooth muscle.
Function
The functions of caveolins are still under intensive investigation. They are best known for their role in the formation of 50-nanometer-size invaginations of the plasma membrane, called caveolae. Oligomers of caveolin form the coat of these domains. Cells that lack caveolins also lack caveolae. Many functions are ascribed to these domains, ranging from endocytosis and transcytosis to signal transduction.
Caveolin-1 has also been shown to play a role in the integrin signaling. The tyrosine phosphorylated form of caveolin-1 colocalizes with focal adhesions, suggesting a role for caveolin-1 in migration. Indeed, downregulation of caveolin-1 leads to less efficient migration in vitro.
Genetically engineered mice that lack caveolin-1 and caveolin-2 are viable and fertile, showing that neither the caveolins nor the caveolae are essential in embryonic development or reproduction of these animals. However, knock-out animals do develop abnormal, hypertrophic lungs, and cardiac myopathy, leading to a reduction in lifespan. Mice lacking caveolins also suffer from impaired angiogenic responses as well as abnormal responses to vasoconstrictive stimuli. In zebrafish, lack of caveolins leads to embryonic lethality, suggesting that higher vertebrates (as exemplified by mice) have developed compensation or redundancy for the functions of caveolins.
Role in disease
Cancer
Caveolins have a paradoxical role in the development of this disease. They have been implicated in both tumor suppression and oncogenesis.[4] High expression of caveolins leads to inhibition of cancer-related pathways, such as growth factor signaling pathways. However, certain cancer cells that express caveolins have been shown to be more aggressive and metastatic, because of a potential for anchorage-independent growth.
Cardiovascular diseases
Caveolins are thought to play an important role during the development of atherosclerosis.[5] Furthermore, caveolin-3 has been associated with Long QT syndrome.[6]
Muscular dystrophy
Caveolin-3 has been implicated in the development of certain types of muscular dystrophy (Limb-girdle muscular dystrophy).[7]
References
- ^ Tang Z, Scherer PE, Okamoto T, Song K, Chu C, Kohtz DS, Nishimoto I, Lodish HF, Lisanti MP (January 1996). "Molecular cloning of caveolin-3, a novel member of the caveolin gene family expressed predominantly in muscle". J. Biol. Chem. 271 (4): 2255–61. doi:10.1074/jbc.271.4.2255. PMID 8567687.
- ^ Scherer PE, Okamoto T, Chun M, Nishimoto I, Lodish HF, Lisanti MP (January 1996). "Identification, sequence, and expression of caveolin-2 defines a caveolin gene family". Proc. Natl. Acad. Sci. U.S.A. 93 (1): 131–5. doi:10.1073/pnas.93.1.131. PMC 40192
. PMID 8552590. - ^ Williams TM, Lisanti MP (2004). "The caveolin proteins". Genome Biol. 5 (3): 214. doi:10.1186/gb-2004-5-3-214. PMC 395759. PMID 15003112.
- ^ Shatz M, Liscovitch M (March 2008). "Caveolin-1: a tumor-promoting role in human cancer". Int. J. Radiat. Biol. 84 (3): 177–89. doi:10.1080/09553000701745293. PMID 18300018.
- ^ Williams TM, Lisanti MP (2004). "The Caveolin genes: from cell biology to medicine". Ann. Med. 36 (8): 584–95. doi:10.1080/07853890410018899. PMID 15768830.
- ^ Vatta M, Ackerman MJ, Ye B, Makielski JC, Ughanze EE, Taylor EW, Tester DJ, Balijepalli RC, Foell JD, Li Z, Kamp TJ, Towbin JA (November 2006). "Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome". Circulation. 114 (20): 2104–12. doi:10.1161/CIRCULATIONAHA.106.635268. PMID 17060380.
- ^ Galbiati F, Razani B, Lisanti MP (October 2001). "Caveolae and caveolin-3 in muscular dystrophy". Trends Mol Med. 7 (10): 435–41. doi:10.1016/S1471-4914(01)02105-0. PMID 11597517.
External links
- The Caveolin Protein
- Caveolins at the US National Library of Medicine Medical Subject Headings (MeSH)
- Caveolin-3 page
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Caveolin Provide feedback
All three known Caveolin forms have the FEDVIAEP caveolin 'signature motif' within their hydrophilic N-terminal domain. Caveolin 2 (Cav-2) is co-localised and co-expressed with Cav-1/VIP21, forms heterodimers with it and needs Cav-1 for proper membrane localisation. Cav-3 has greater protein sequence similarity to Cav-1 than to Cav-2. Cellular processes caveolins are involved in include vesicular transport, cholesterol homeostasis, signal transduction, and tumour suppression [1].
Literature references
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Williams TM, Lisanti MP; , Genome Biol 2004;5:214.: The caveolin proteins. PUBMED:15003112 EPMC:15003112
External database links
| PROSITE: | PDOC00930 |
This tab holds annotation information from the InterPro database.
InterPro entry IPR001612
Caveolae are 50-100 nm invaginations located at the plasma membrane of many cell types and are known to transport molecules across endothelial cells [PUBMED:9759488]. Caveolae require the caveolin protein for formation. Caveolins may act as scaffolding proteins within caveolar membranes by compartmentalizing and concentrating signalling molecules. Mammals have three caveolin proteins:caveolin-1 (Cav-1, or VIP21), caveolin-2 and caveolin-3 (or M-caveolin). Various classes of signalling molecules, including G-protein subunits, receptor and non-receptor tyrosine kinases, endothelial nitric oxide synthase (eNOS), and small GTPases, bind Cav-1 through its 'caveolin-scaffolding domain' [PUBMED:23028656].
Caveolins are proteins of about 20 Kd, they form high molecular mass homo-oligomers. Structurally they seem to have N-terminal and C-terminal hydrophilic segments and a long central transmembrane domain that probably forms a hairpin in the membrane. Both extremities are known to face the cytoplasm. Caveolae are enriched with cholesterol and Cav-1 is one of the few proteins that binds cholesterol tightly and specifically.
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Biological process | caveola assembly (GO:0070836) |
Domain organisation
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Alignments
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| Seed (39) |
Full (662) |
Representative proteomes | UniProt (1009) |
NCBI (1561) |
Meta (0) |
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| RP15 (208) |
RP35 (346) |
RP55 (554) |
RP75 (626) |
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| PP/heatmap | 1 | ||||||||
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| Seed (39) |
Full (662) |
Representative proteomes | UniProt (1009) |
NCBI (1561) |
Meta (0) |
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|---|---|---|---|---|---|---|---|---|---|
| RP15 (208) |
RP35 (346) |
RP55 (554) |
RP75 (626) |
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| Raw Stockholm | |||||||||
| Gzipped | |||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Prosite |
| Previous IDs: | none |
| Type: | Family |
| Sequence Ontology: | SO:0100021 |
| Author: |
Finn RD  , Bateman A
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| Number in seed: | 39 |
| Number in full: | 662 |
| Average length of the domain: | 127.30 aa |
| Average identity of full alignment: | 40 % |
| Average coverage of the sequence by the domain: | 59.56 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 133 | ||||||||||||
| Family (HMM) version: | 17 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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